The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future.
Identifieur interne : 001986 ( Main/Exploration ); précédent : 001985; suivant : 001987The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future.
Auteurs : Susan H. Fox [Canada] ; Jonathan M. BrotchieSource :
- Progress in brain research [ 1875-7855 ] ; 2010.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (toxicity), Basal Ganglia (pathology), Cognition Disorders (chemically induced), Cognition Disorders (psychology), Disease Models, Animal, Dopamine (physiology), Drug Discovery, Endpoint Determination, Humans, Levodopa (toxicity), MPTP Poisoning (pathology), MPTP Poisoning (psychology), Movement (physiology), Neurons (pathology), Neuroprotective Agents (pharmacology), Parkinson Disease, Secondary (chemically induced), Parkinson Disease, Secondary (pathology), Parkinson Disease, Secondary (psychology), Primates, Psychoses, Substance-Induced (etiology), Psychoses, Substance-Induced (psychology), Sleep Wake Disorders (chemically induced), Sleep Wake Disorders (psychology), alpha-Synuclein (genetics), alpha-Synuclein (physiology).
- MESH :
- chemical , genetics : alpha-Synuclein.
- chemical , pharmacology : Neuroprotective Agents.
- chemical , physiology : Dopamine, alpha-Synuclein.
- chemical , toxicity : Antiparkinson Agents, Levodopa.
- chemically induced : Cognition Disorders, Parkinson Disease, Secondary, Sleep Wake Disorders.
- etiology : Psychoses, Substance-Induced.
- pathology : Basal Ganglia, MPTP Poisoning, Neurons, Parkinson Disease, Secondary.
- physiology : Movement.
- psychology : Cognition Disorders, MPTP Poisoning, Parkinson Disease, Secondary, Psychoses, Substance-Induced, Sleep Wake Disorders.
- Animals, Disease Models, Animal, Drug Discovery, Endpoint Determination, Humans, Primates.
Abstract
Non-human primate (NHP) models of Parkinson's disease (PD) have been essential in understanding the pathophysiology and neural mechanisms underlying PD. The most common toxin employed, MPTP, produces a parkinsonian phenotype in NHPs that is very similar to human PD with excellent response to dopaminergic drugs and development of long-term motor complications. Over the past 25 years, MPTP-lesioned NHP models, using several species and a variety of MPTP administration regimens, have been used to understand disease pathophysiology, investigate several stages of the disease progression, from pre-symptomatic to advanced with motor complications, and apply knowledge gained to develop potential therapeutics. Many treatments in common use in PD patients were developed on the basis of studies in the MPTP model, in particular dopamine agonists, amantadine, and targeting the subthalamic nucleus for surgical treatment of PD. Continued development of novel therapies for PD will require improving methods of evaluating symptoms in NHPs to ease translation from NHP to patients with homogenized scales and endpoints. In addition, recent studies into non-motor symptoms of PD, especially in response to chronic treatment, is expanding the usefulness and impact of MPTP-lesioned NHP models. Despite these obvious successes, limitations still exist in the model, particularly when considering underlying mechanisms of disease progression; thus, it appears difficult to reliably use acute toxin administration to replicate a chronic progressive disorder and provide consistent evidence of Lewy-like bodies.
DOI: 10.1016/S0079-6123(10)84007-5
PubMed: 20887873
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream PubMed, to step Corpus: 000D99
- to stream PubMed, to step Curation: 000D99
- to stream PubMed, to step Checkpoint: 000D99
- to stream Ncbi, to step Merge: 000D46
- to stream Ncbi, to step Curation: 000D46
- to stream Ncbi, to step Checkpoint: 000D46
- to stream Main, to step Merge: 001A90
- to stream Main, to step Curation: 001986
Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future.</title><author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name><affiliation wicri:level="4"><nlm:affiliation>Division of Neurology, University of Toronto, Ontario, Canada. sfox@uhnresearch.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2010">2010</date><idno type="RBID">pubmed:20887873</idno><idno type="pmid">20887873</idno><idno type="doi">10.1016/S0079-6123(10)84007-5</idno><idno type="wicri:Area/PubMed/Corpus">000D99</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000D99</idno><idno type="wicri:Area/PubMed/Curation">000D99</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000D99</idno><idno type="wicri:Area/PubMed/Checkpoint">000D99</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000D99</idno><idno type="wicri:Area/Ncbi/Merge">000D46</idno><idno type="wicri:Area/Ncbi/Curation">000D46</idno><idno type="wicri:Area/Ncbi/Checkpoint">000D46</idno><idno type="wicri:Area/Main/Merge">001A90</idno><idno type="wicri:Area/Main/Curation">001986</idno><idno type="wicri:Area/Main/Exploration">001986</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future.</title><author><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name><affiliation wicri:level="4"><nlm:affiliation>Division of Neurology, University of Toronto, Ontario, Canada. sfox@uhnresearch.ca</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, University of Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name></author></analytic><series><title level="j">Progress in brain research</title><idno type="eISSN">1875-7855</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiparkinson Agents (toxicity)</term><term>Basal Ganglia (pathology)</term><term>Cognition Disorders (chemically induced)</term><term>Cognition Disorders (psychology)</term><term>Disease Models, Animal</term><term>Dopamine (physiology)</term><term>Drug Discovery</term><term>Endpoint Determination</term><term>Humans</term><term>Levodopa (toxicity)</term><term>MPTP Poisoning (pathology)</term><term>MPTP Poisoning (psychology)</term><term>Movement (physiology)</term><term>Neurons (pathology)</term><term>Neuroprotective Agents (pharmacology)</term><term>Parkinson Disease, Secondary (chemically induced)</term><term>Parkinson Disease, Secondary (pathology)</term><term>Parkinson Disease, Secondary (psychology)</term><term>Primates</term><term>Psychoses, Substance-Induced (etiology)</term><term>Psychoses, Substance-Induced (psychology)</term><term>Sleep Wake Disorders (chemically induced)</term><term>Sleep Wake Disorders (psychology)</term><term>alpha-Synuclein (genetics)</term><term>alpha-Synuclein (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Neuroprotective Agents</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Dopamine</term><term>alpha-Synuclein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="toxicity" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Cognition Disorders</term><term>Parkinson Disease, Secondary</term><term>Sleep Wake Disorders</term></keywords><keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Psychoses, Substance-Induced</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Basal Ganglia</term><term>MPTP Poisoning</term><term>Neurons</term><term>Parkinson Disease, Secondary</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Movement</term></keywords><keywords scheme="MESH" qualifier="psychology" xml:lang="en"><term>Cognition Disorders</term><term>MPTP Poisoning</term><term>Parkinson Disease, Secondary</term><term>Psychoses, Substance-Induced</term><term>Sleep Wake Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Drug Discovery</term><term>Endpoint Determination</term><term>Humans</term><term>Primates</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Non-human primate (NHP) models of Parkinson's disease (PD) have been essential in understanding the pathophysiology and neural mechanisms underlying PD. The most common toxin employed, MPTP, produces a parkinsonian phenotype in NHPs that is very similar to human PD with excellent response to dopaminergic drugs and development of long-term motor complications. Over the past 25 years, MPTP-lesioned NHP models, using several species and a variety of MPTP administration regimens, have been used to understand disease pathophysiology, investigate several stages of the disease progression, from pre-symptomatic to advanced with motor complications, and apply knowledge gained to develop potential therapeutics. Many treatments in common use in PD patients were developed on the basis of studies in the MPTP model, in particular dopamine agonists, amantadine, and targeting the subthalamic nucleus for surgical treatment of PD. Continued development of novel therapies for PD will require improving methods of evaluating symptoms in NHPs to ease translation from NHP to patients with homogenized scales and endpoints. In addition, recent studies into non-motor symptoms of PD, especially in response to chronic treatment, is expanding the usefulness and impact of MPTP-lesioned NHP models. Despite these obvious successes, limitations still exist in the model, particularly when considering underlying mechanisms of disease progression; thus, it appears difficult to reliably use acute toxin administration to replicate a chronic progressive disorder and provide consistent evidence of Lewy-like bodies.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><noCountry><name sortKey="Brotchie, Jonathan M" sort="Brotchie, Jonathan M" uniqKey="Brotchie J" first="Jonathan M" last="Brotchie">Jonathan M. Brotchie</name></noCountry><country name="Canada"><region name="Ontario"><name sortKey="Fox, Susan H" sort="Fox, Susan H" uniqKey="Fox S" first="Susan H" last="Fox">Susan H. Fox</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001986 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 001986 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Canada
|area= ParkinsonCanadaV1
|flux= Main
|étape= Exploration
|type= RBID
|clé= pubmed:20887873
|texte= The MPTP-lesioned non-human primate models of Parkinson's disease. Past, present, and future.
}}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:20887873" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |