Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease
Identifieur interne : 000089 ( Ncbi/Merge ); précédent : 000088; suivant : 000090Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease
Auteurs : Andreas Hartmann [France] ; Stéphane Hunot [France] ; Patrick P. Michel [France] ; Marie-Paule Muriel [France] ; Sheela Vyas [Royaume-Uni] ; Baptiste A. Faucheux [France] ; Annick Mouatt-Prigent [France] ; Hélène Turmel [France] ; Anu Srinivasan [États-Unis] ; Merle Ruberg [France] ; Gerard I. Evan [Royaume-Uni] ; Yves Agid [France] ; Etienne C. Hirsch [France]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2000.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology), Aged, Aged, 80 and over, Animals, Apoptosis, Blotting, Western, Brain (enzymology), Brain (ultrastructure), Caspase 3, Caspases (biosynthesis), Caspases (physiology), Cells, Cultured, Dopamine (metabolism), Dopamine Agents (pharmacology), Enzyme Activation, Humans, Immunohistochemistry, Male, Mesencephalon (enzymology), Mice, Mice, Inbred C57BL, Neurons (enzymology), Neurons (ultrastructure), Parkinson Disease (enzymology), Parkinson Disease (metabolism), Rats, Substantia Nigra (enzymology), Tissue Distribution, Ventral Tegmental Area (enzymology).
- MESH :
- chemical , biosynthesis : Caspases.
- chemical , metabolism : Dopamine.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine Agents.
- enzymology : Brain, Mesencephalon, Neurons, Parkinson Disease, Substantia Nigra, Ventral Tegmental Area.
- metabolism : Parkinson Disease.
- chemical , physiology : Caspases.
- ultrastructure : Brain, Neurons.
- Aged, Aged, 80 and over, Animals, Apoptosis, Blotting, Western, Caspase 3, Cells, Cultured, Enzyme Activation, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred C57BL, Rats, Tissue Distribution.
Abstract
Caspase-3 is an effector of apoptosis in experimental
models of Parkinson's disease (PD). However, its potential role in the
human pathology remains to be demonstrated. Using caspase-3
immunohistochemistry on the postmortem human brain, we observed a
positive correlation between the degree of neuronal loss in
dopaminergic (DA) cell groups affected in the mesencephalon of PD
patients and the percentage of caspase-3-positive neurons in these cell
groups in control subjects and a significant decrease of
caspase-3-positive pigmented neurons in the substantia nigra pars
compacta of PD patients compared with controls that also could be
observed in an animal model of PD. This suggests that neurons
expressing caspase-3 are more sensitive to the pathological process
than those that do not express the protein. In addition, using an
antibody raised against activated caspase-3, the percentage of active
caspase-3-positive neurons among DA neurons was significantly higher in
PD patients than in controls. Finally, electron microscopy analysis in
the human brain and
Url:
PubMed: 10688892
PubMed Central: 16023
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PMC:16023Le document en format XML
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apoptotic death of dopaminergic neurons in
Parkinson's disease</title><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Muriel, Marie Paule" sort="Muriel, Marie Paule" uniqKey="Muriel M" first="Marie-Paule" last="Muriel">Marie-Paule Muriel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vyas, Sheela" sort="Vyas, Sheela" uniqKey="Vyas S" first="Sheela" last="Vyas">Sheela Vyas</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Faucheux, Baptiste A" sort="Faucheux, Baptiste A" uniqKey="Faucheux B" first="Baptiste A." last="Faucheux">Baptiste A. Faucheux</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mouatt Prigent, Annick" sort="Mouatt Prigent, Annick" uniqKey="Mouatt Prigent A" first="Annick" last="Mouatt-Prigent">Annick Mouatt-Prigent</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Turmel, Helene" sort="Turmel, Helene" uniqKey="Turmel H" first="Hélène" last="Turmel">Hélène Turmel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Srinivasan, Anu" sort="Srinivasan, Anu" uniqKey="Srinivasan A" first="Anu" last="Srinivasan">Anu Srinivasan</name><affiliation wicri:level="2"><nlm:aff id="N0x9ea9268.0xa03f080">IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Evan, Gerard I" sort="Evan, Gerard I" uniqKey="Evan G" first="Gerard I." last="Evan">Gerard I. Evan</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2000">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Apoptosis</term><term>Blotting, Western</term><term>Brain (enzymology)</term><term>Brain (ultrastructure)</term><term>Caspase 3</term><term>Caspases (biosynthesis)</term><term>Caspases (physiology)</term><term>Cells, Cultured</term><term>Dopamine (metabolism)</term><term>Dopamine Agents (pharmacology)</term><term>Enzyme Activation</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mesencephalon (enzymology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neurons (enzymology)</term><term>Neurons (ultrastructure)</term><term>Parkinson Disease (enzymology)</term><term>Parkinson Disease (metabolism)</term><term>Rats</term><term>Substantia Nigra (enzymology)</term><term>Tissue Distribution</term><term>Ventral Tegmental Area (enzymology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Dopamine Agents</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term><term>Mesencephalon</term><term>Neurons</term><term>Parkinson Disease</term><term>Substantia Nigra</term><term>Ventral Tegmental Area</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Brain</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Apoptosis</term><term>Blotting, Western</term><term>Caspase 3</term><term>Cells, Cultured</term><term>Enzyme Activation</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Rats</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Caspase-3 is an effector of apoptosis in experimental
models of Parkinson's disease (PD). However, its potential role in the
human pathology remains to be demonstrated. Using caspase-3
immunohistochemistry on the postmortem human brain, we observed a
positive correlation between the degree of neuronal loss in
dopaminergic (DA) cell groups affected in the mesencephalon of PD
patients and the percentage of caspase-3-positive neurons in these cell
groups in control subjects and a significant decrease of
caspase-3-positive pigmented neurons in the substantia nigra pars
compacta of PD patients compared with controls that also could be
observed in an animal model of PD. This suggests that neurons
expressing caspase-3 are more sensitive to the pathological process
than those that do not express the protein. In addition, using an
antibody raised against activated caspase-3, the percentage of active
caspase-3-positive neurons among DA neurons was significantly higher in
PD patients than in controls. Finally, electron microscopy analysis in
the human brain and <italic>in vitro</italic> data suggest that caspase-3
activation precedes and is not a consequence of apoptotic cell
death in PD.</p></div></front></TEI><double pmid="10688892"><pmc><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Caspase-3: A vulnerability factor and final effector in
apoptotic death of dopaminergic neurons in
Parkinson's disease</title><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Muriel, Marie Paule" sort="Muriel, Marie Paule" uniqKey="Muriel M" first="Marie-Paule" last="Muriel">Marie-Paule Muriel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vyas, Sheela" sort="Vyas, Sheela" uniqKey="Vyas S" first="Sheela" last="Vyas">Sheela Vyas</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Faucheux, Baptiste A" sort="Faucheux, Baptiste A" uniqKey="Faucheux B" first="Baptiste A." last="Faucheux">Baptiste A. Faucheux</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mouatt Prigent, Annick" sort="Mouatt Prigent, Annick" uniqKey="Mouatt Prigent A" first="Annick" last="Mouatt-Prigent">Annick Mouatt-Prigent</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Turmel, Helene" sort="Turmel, Helene" uniqKey="Turmel H" first="Hélène" last="Turmel">Hélène Turmel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Srinivasan, Anu" sort="Srinivasan, Anu" uniqKey="Srinivasan A" first="Anu" last="Srinivasan">Anu Srinivasan</name><affiliation wicri:level="2"><nlm:aff id="N0x9ea9268.0xa03f080">IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Evan, Gerard I" sort="Evan, Gerard I" uniqKey="Evan G" first="Gerard I." last="Evan">Gerard I. Evan</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">10688892</idno><idno type="pmc">16023</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC16023</idno><idno type="RBID">PMC:16023</idno><date when="2000">2000</date><idno type="wicri:Area/Pmc/Corpus">000214</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000214</idno><idno type="wicri:Area/Pmc/Curation">000212</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000212</idno><idno type="wicri:Area/Pmc/Checkpoint">000940</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000940</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Caspase-3: A vulnerability factor and final effector in
apoptotic death of dopaminergic neurons in
Parkinson's disease</title><author><name sortKey="Hartmann, Andreas" sort="Hartmann, Andreas" uniqKey="Hartmann A" first="Andreas" last="Hartmann">Andreas Hartmann</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, Stephane" sort="Hunot, Stephane" uniqKey="Hunot S" first="Stéphane" last="Hunot">Stéphane Hunot</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Michel, Patrick P" sort="Michel, Patrick P" uniqKey="Michel P" first="Patrick P." last="Michel">Patrick P. Michel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Muriel, Marie Paule" sort="Muriel, Marie Paule" uniqKey="Muriel M" first="Marie-Paule" last="Muriel">Marie-Paule Muriel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Vyas, Sheela" sort="Vyas, Sheela" uniqKey="Vyas S" first="Sheela" last="Vyas">Sheela Vyas</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Faucheux, Baptiste A" sort="Faucheux, Baptiste A" uniqKey="Faucheux B" first="Baptiste A." last="Faucheux">Baptiste A. Faucheux</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Mouatt Prigent, Annick" sort="Mouatt Prigent, Annick" uniqKey="Mouatt Prigent A" first="Annick" last="Mouatt-Prigent">Annick Mouatt-Prigent</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Turmel, Helene" sort="Turmel, Helene" uniqKey="Turmel H" first="Hélène" last="Turmel">Hélène Turmel</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Srinivasan, Anu" sort="Srinivasan, Anu" uniqKey="Srinivasan A" first="Anu" last="Srinivasan">Anu Srinivasan</name><affiliation wicri:level="2"><nlm:aff id="N0x9ea9268.0xa03f080">IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla, CA 92037</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">Californie</region></placeName><wicri:cityArea>IDUN Pharmaceuticals Inc., 11085 North Pines Road, La Jolla</wicri:cityArea></affiliation></author><author><name sortKey="Ruberg, Merle" sort="Ruberg, Merle" uniqKey="Ruberg M" first="Merle" last="Ruberg">Merle Ruberg</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Evan, Gerard I" sort="Evan, Gerard I" uniqKey="Evan G" first="Gerard I." last="Evan">Gerard I. Evan</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="N0x9ea9268.0xa03f080">Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX, United Kingdom</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Imperial Cancer Research Fund Laboratories, 44 Lincoln's Inn Field, London WC2A 3PX</wicri:regionArea><wicri:noRegion>London WC2A 3PX</wicri:noRegion></affiliation></author><author><name sortKey="Agid, Yves" sort="Agid, Yves" uniqKey="Agid Y" first="Yves" last="Agid">Yves Agid</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Hirsch, Etienne C" sort="Hirsch, Etienne C" uniqKey="Hirsch E" first="Etienne C." last="Hirsch">Etienne C. Hirsch</name><affiliation wicri:level="3"><nlm:aff id="N0x9ea9268.0xa03f080">Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris, France;</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l′Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2000">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Caspase-3 is an effector of apoptosis in experimental
models of Parkinson's disease (PD). However, its potential role in the
human pathology remains to be demonstrated. Using caspase-3
immunohistochemistry on the postmortem human brain, we observed a
positive correlation between the degree of neuronal loss in
dopaminergic (DA) cell groups affected in the mesencephalon of PD
patients and the percentage of caspase-3-positive neurons in these cell
groups in control subjects and a significant decrease of
caspase-3-positive pigmented neurons in the substantia nigra pars
compacta of PD patients compared with controls that also could be
observed in an animal model of PD. This suggests that neurons
expressing caspase-3 are more sensitive to the pathological process
than those that do not express the protein. In addition, using an
antibody raised against activated caspase-3, the percentage of active
caspase-3-positive neurons among DA neurons was significantly higher in
PD patients than in controls. Finally, electron microscopy analysis in
the human brain and <italic>in vitro</italic> data suggest that caspase-3
activation precedes and is not a consequence of apoptotic cell
death in PD.</p></div></front></TEI></pmc><pubmed><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease.</title><author><name sortKey="Hartmann, A" sort="Hartmann, A" uniqKey="Hartmann A" first="A" last="Hartmann">A. Hartmann</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, S" sort="Hunot, S" uniqKey="Hunot S" first="S" last="Hunot">S. Hunot</name></author><author><name sortKey="Michel, P P" sort="Michel, P P" uniqKey="Michel P" first="P P" last="Michel">P P Michel</name></author><author><name sortKey="Muriel, M P" sort="Muriel, M P" uniqKey="Muriel M" first="M P" last="Muriel">M P Muriel</name></author><author><name sortKey="Vyas, S" sort="Vyas, S" uniqKey="Vyas S" first="S" last="Vyas">S. Vyas</name></author><author><name sortKey="Faucheux, B A" sort="Faucheux, B A" uniqKey="Faucheux B" first="B A" last="Faucheux">B A Faucheux</name></author><author><name sortKey="Mouatt Prigent, A" sort="Mouatt Prigent, A" uniqKey="Mouatt Prigent A" first="A" last="Mouatt-Prigent">A. Mouatt-Prigent</name></author><author><name sortKey="Turmel, H" sort="Turmel, H" uniqKey="Turmel H" first="H" last="Turmel">H. Turmel</name></author><author><name sortKey="Srinivasan, A" sort="Srinivasan, A" uniqKey="Srinivasan A" first="A" last="Srinivasan">A. Srinivasan</name></author><author><name sortKey="Ruberg, M" sort="Ruberg, M" uniqKey="Ruberg M" first="M" last="Ruberg">M. Ruberg</name></author><author><name sortKey="Evan, G I" sort="Evan, G I" uniqKey="Evan G" first="G I" last="Evan">G I Evan</name></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y" last="Agid">Yves Agid</name><affiliation><country>France</country><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName><country>France</country><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E C" last="Hirsch">E C Hirsch</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2000">2000</date><idno type="RBID">pubmed:10688892</idno><idno type="pmid">10688892</idno><idno type="doi">10.1073/pnas.040556597</idno><idno type="wicri:Area/PubMed/Corpus">001338</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001338</idno><idno type="wicri:Area/PubMed/Curation">001297</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001297</idno><idno type="wicri:Area/PubMed/Checkpoint">001297</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">001297</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Caspase-3: A vulnerability factor and final effector in apoptotic death of dopaminergic neurons in Parkinson's disease.</title><author><name sortKey="Hartmann, A" sort="Hartmann, A" uniqKey="Hartmann A" first="A" last="Hartmann">A. Hartmann</name><affiliation wicri:level="3"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale U 289, Hôpital de la Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris</wicri:regionArea><placeName><region type="region" nuts="2">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Hunot, S" sort="Hunot, S" uniqKey="Hunot S" first="S" last="Hunot">S. Hunot</name></author><author><name sortKey="Michel, P P" sort="Michel, P P" uniqKey="Michel P" first="P P" last="Michel">P P Michel</name></author><author><name sortKey="Muriel, M P" sort="Muriel, M P" uniqKey="Muriel M" first="M P" last="Muriel">M P Muriel</name></author><author><name sortKey="Vyas, S" sort="Vyas, S" uniqKey="Vyas S" first="S" last="Vyas">S. Vyas</name></author><author><name sortKey="Faucheux, B A" sort="Faucheux, B A" uniqKey="Faucheux B" first="B A" last="Faucheux">B A Faucheux</name></author><author><name sortKey="Mouatt Prigent, A" sort="Mouatt Prigent, A" uniqKey="Mouatt Prigent A" first="A" last="Mouatt-Prigent">A. Mouatt-Prigent</name></author><author><name sortKey="Turmel, H" sort="Turmel, H" uniqKey="Turmel H" first="H" last="Turmel">H. Turmel</name></author><author><name sortKey="Srinivasan, A" sort="Srinivasan, A" uniqKey="Srinivasan A" first="A" last="Srinivasan">A. Srinivasan</name></author><author><name sortKey="Ruberg, M" sort="Ruberg, M" uniqKey="Ruberg M" first="M" last="Ruberg">M. Ruberg</name></author><author><name sortKey="Evan, G I" sort="Evan, G I" uniqKey="Evan G" first="G I" last="Evan">G I Evan</name></author><author><name sortKey="Agid, Y" sort="Agid, Y" uniqKey="Agid Y" first="Y" last="Agid">Yves Agid</name><affiliation><country>France</country><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName><country>France</country><placeName><settlement type="city">Paris</settlement><region type="region" nuts="2">Île-de-France</region></placeName><orgName type="hospital" n="4">Hôpital de la Salpêtrière</orgName></affiliation></author><author><name sortKey="Hirsch, E C" sort="Hirsch, E C" uniqKey="Hirsch E" first="E C" last="Hirsch">E C Hirsch</name></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Apoptosis</term><term>Blotting, Western</term><term>Brain (enzymology)</term><term>Brain (ultrastructure)</term><term>Caspase 3</term><term>Caspases (biosynthesis)</term><term>Caspases (physiology)</term><term>Cells, Cultured</term><term>Dopamine (metabolism)</term><term>Dopamine Agents (pharmacology)</term><term>Enzyme Activation</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mesencephalon (enzymology)</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Neurons (enzymology)</term><term>Neurons (ultrastructure)</term><term>Parkinson Disease (enzymology)</term><term>Parkinson Disease (metabolism)</term><term>Rats</term><term>Substantia Nigra (enzymology)</term><term>Tissue Distribution</term><term>Ventral Tegmental Area (enzymology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term><term>Dopamine Agents</term></keywords><keywords scheme="MESH" qualifier="enzymology" xml:lang="en"><term>Brain</term><term>Mesencephalon</term><term>Neurons</term><term>Parkinson Disease</term><term>Substantia Nigra</term><term>Ventral Tegmental Area</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Caspases</term></keywords><keywords scheme="MESH" qualifier="ultrastructure" xml:lang="en"><term>Brain</term><term>Neurons</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Aged, 80 and over</term><term>Animals</term><term>Apoptosis</term><term>Blotting, Western</term><term>Caspase 3</term><term>Cells, Cultured</term><term>Enzyme Activation</term><term>Humans</term><term>Immunohistochemistry</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Rats</term><term>Tissue Distribution</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Caspase-3 is an effector of apoptosis in experimental models of Parkinson's disease (PD). However, its potential role in the human pathology remains to be demonstrated. Using caspase-3 immunohistochemistry on the postmortem human brain, we observed a positive correlation between the degree of neuronal loss in dopaminergic (DA) cell groups affected in the mesencephalon of PD patients and the percentage of caspase-3-positive neurons in these cell groups in control subjects and a significant decrease of caspase-3-positive pigmented neurons in the substantia nigra pars compacta of PD patients compared with controls that also could be observed in an animal model of PD. This suggests that neurons expressing caspase-3 are more sensitive to the pathological process than those that do not express the protein. In addition, using an antibody raised against activated caspase-3, the percentage of active caspase-3-positive neurons among DA neurons was significantly higher in PD patients than in controls. Finally, electron microscopy analysis in the human brain and in vitro data suggest that caspase-3 activation precedes and is not a consequence of apoptotic cell death in PD.</div></front></TEI></pubmed></double></record>Pour manipuler ce document sous Unix (Dilib)
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