α-Synuclein and Parkinsonism: Updates and Future Perspectives.
Mutations in the SNCA gene, which encodes the α-synuclein protein, were the first discovered genetic causes of familial parkinsonism with Lewy pathology. To date, six different SNCA missense mutations as well as multiplications are known to cause parkinsonism. For this review, we performed a literature search to identify all published cases of SNCA-related parkinsonism to provide an updated summary of the clinical and neuropathological features of parkinsonism due to SNCA mutations. Familial parkinsonism associated with SNCA is rare, but α-synuclein aggregation is a core feature of sporadic parkinsonism, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Research into α-synuclein and parkinsonism has impacted how we define the pathology and understand the pathogenesis of Parkinson's disease and related neurodegenerative disorders. We briefly discuss some of the lessons we have learned from research into the physiological role of α-synuclein and its pathological links to neurodegeneration and parkinsonism.
Krembil Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
Kaie
K
Rosborough
Krembil Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada.
Neha
N
Patel
Krembil Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada. lorraine.kalia@utoronto.ca.|Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Department of Medicine, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. lorraine.kalia@utoronto.ca.|Division of Neurology, Department of Medicine and Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada. lorraine.kalia@utoronto.ca.
Lorraine V
LV
Kalia
D006801:Humans; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
D051844:alpha-Synuclein
Dementia with Lewy bodies; Lewy pathology; Multiple system atrophy; Parkinson’s disease; Phenotype; SNCA