Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease.
Identifieur interne : 000675 ( Main/Exploration ); précédent : 000674; suivant : 000676Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease.
Auteurs : Mattia Volta [Canada] ; Austen J. Milnerwood [Canada] ; Matthew J. Farrer [Canada]Source :
- The Lancet. Neurology [ 1474-4465 ] ; 2015.
English descriptors
- KwdEn :
- MESH :
- genetics : Parkinson Disease.
- metabolism : Parkinson Disease.
- therapy : Parkinson Disease.
- Animals, Humans.
Abstract
Disease-modifying therapies that slow or halt the progression of Parkinson's disease are an unmet clinical need. Many hypotheses have been put forward to explain the pathogenesis of the disease, but none has led to the development of disease-modifying drugs. Here we focus on familial forms of late-onset parkinsonism that most closely resemble idiopathic Parkinson's disease and present a synthesis of emerging molecular advances. Genetic discoveries and mechanistic investigations have highlighted early alterations to synaptic function, endosomal maturation, and protein sorting that might lead to an intracellular proteinopathy. We propose that these cellular processes constitute one pathway to pathogenesis and suggest that neuroprotection, as an adjunct to current symptomatic treatments, need not remain an elusive goal.
DOI: 10.1016/S1474-4422(15)00186-6
PubMed: 26376970
Affiliations:
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Le document en format XML
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Milnerwood</name><affiliation wicri:level="1"><nlm:affiliation>Division of Neurology, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Division of Neurology, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medical Genetics, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. 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Many hypotheses have been put forward to explain the pathogenesis of the disease, but none has led to the development of disease-modifying drugs. Here we focus on familial forms of late-onset parkinsonism that most closely resemble idiopathic Parkinson's disease and present a synthesis of emerging molecular advances. Genetic discoveries and mechanistic investigations have highlighted early alterations to synaptic function, endosomal maturation, and protein sorting that might lead to an intracellular proteinopathy. 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