title: Insights from late-onset familial parkinsonism on the pathogenesis of idiopathic Parkinson's disease.
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.
authors.affiliation: Department of Medical Genetics, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Mattia
authors.initials: M
authors.lastname: Volta
authors.affiliation: Division of Neurology, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Austen J
authors.initials: AJ
authors.lastname: Milnerwood
authors.affiliation: Department of Medical Genetics, Centre for Applied Neurogenetics, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada. Electronic address: mfarrer@can.ubc.ca.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000818:Animals; D006801:Humans; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000628:therapy