Parkinson's Disease
Identifieur interne : 000A03 ( Main/Exploration ); précédent : 000A02; suivant : 000A04Parkinson's Disease
Auteurs : Christopher H. Hawkes [Royaume-Uni] ; Kelly Del Tredici [Allemagne] ; Heiko Braak [Allemagne]Source :
- Annals of the New York Academy of SciencesInternational Symposium on Olfaction and Taste [ 0077-8923 ] ; 2009-07.
English descriptors
Abstract
Accumulating evidence suggests that sporadic Parkinson's disease (sPD) has a long prodromal period during which several nonmotor features develop; in particular, impairment of olfaction, vagal dysfunction, and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexuses of the foregut. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (a) nasal, with anterograde progression into the temporal lobe; and (b) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and via transsynaptic transmission reach the preganglionic parasympathetic motor neurons of the vagus nerve. This would allow retrograde transport into the medulla and from here into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sPD is pathogenic access to the brain through the foregut and nose—hence the term “dual hit.”
Url:
DOI: 10.1111/j.1749-6632.2009.04365.x
Affiliations:
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Hawkes</name><affiliation wicri:level="3"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Del Tredici, Kelly" sort="Del Tredici, Kelly" uniqKey="Del Tredici K" first="Kelly" last="Del Tredici">Kelly Del Tredici</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Clinical Neuroanatomy, Johann Wolfgang Goethe University, Frankfurt am Main</wicri:regionArea><wicri:noRegion>Frankfurt am Main</wicri:noRegion><wicri:noRegion>Frankfurt am Main</wicri:noRegion></affiliation></author><author><name sortKey="Braak, Heiko" sort="Braak, Heiko" uniqKey="Braak H" first="Heiko" last="Braak">Heiko Braak</name><affiliation wicri:level="1"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute for Clinical Neuroanatomy, Johann Wolfgang Goethe University, Frankfurt am Main</wicri:regionArea><wicri:noRegion>Frankfurt am Main</wicri:noRegion><wicri:noRegion>Frankfurt am Main</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of the New York Academy of SciencesInternational Symposium on Olfaction and Taste</title><idno type="ISSN">0077-8923</idno><idno type="eISSN">1749-6632</idno><imprint><publisher>Blackwell Publishing Inc</publisher><pubPlace>Malden, USA</pubPlace><date type="published" when="2009-07">2009-07</date><biblScope unit="volume">1170</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="615">615</biblScope><biblScope unit="page" to="622">622</biblScope></imprint><idno type="ISSN">0077-8923</idno></series><idno type="istex">ED26D936F8870CA85C45D8EEF8672560B9A46C5D</idno><idno type="DOI">10.1111/j.1749-6632.2009.04365.x</idno><idno type="ArticleID">NYAS04365</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0077-8923</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Parkinson's disease</term><term>alpha‐synuclein</term><term>autonomic regulation</term><term>etiology</term><term>olfaction</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Accumulating evidence suggests that sporadic Parkinson's disease (sPD) has a long prodromal period during which several nonmotor features develop; in particular, impairment of olfaction, vagal dysfunction, and sleep disorder. Early sites of Lewy pathology are the olfactory bulb and enteric plexuses of the foregut. We propose that a neurotropic pathogen, probably viral, enters the brain via two routes: (a) nasal, with anterograde progression into the temporal lobe; and (b) gastric, secondary to swallowing of nasal secretions in saliva. These secretions might contain a neurotropic pathogen that, after penetration of the epithelial lining, could enter axons of the Meissner's plexus and via transsynaptic transmission reach the preganglionic parasympathetic motor neurons of the vagus nerve. This would allow retrograde transport into the medulla and from here into the pons and midbrain until the substantia nigra is reached and typical aspects of disease commence. Evidence for this theory from the perspective of olfactory and autonomic dysfunction is reviewed and the possible routes of pathogenic invasion are considered. It is concluded that the most parsimonious explanation for the initial events of sPD is pathogenic access to the brain through the foregut and nose—hence the term “dual hit.”</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Hawkes, Christopher H" sort="Hawkes, Christopher H" uniqKey="Hawkes C" first="Christopher H." last="Hawkes">Christopher H. Hawkes</name></region></country><country name="Allemagne"><noRegion><name sortKey="Del Tredici, Kelly" sort="Del Tredici, Kelly" uniqKey="Del Tredici K" first="Kelly" last="Del Tredici">Kelly Del Tredici</name></noRegion><name sortKey="Braak, Heiko" sort="Braak, Heiko" uniqKey="Braak H" first="Heiko" last="Braak">Heiko Braak</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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