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α-Synuclein and Parkinsonism: Updates and Future Perspectives

  • Movement Disorders (S Fox, Section Editor)
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Abstract

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.

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Acknowledgements

We thank Megha Duggal for proofreading the manuscript and tables.

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Authors and Affiliations

  1. Krembil Research Institute, Toronto Western Hospital, University Health Network, 399 Bathurst Street, Toronto, ON, M5T 2S8, Canada

    Kaie Rosborough, Neha Patel & Lorraine V. Kalia

  2. 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 V. Kalia

  3. Division of Neurology, Department of Medicine and Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada

    Lorraine V. Kalia

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  1. Kaie Rosborough
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  2. Neha Patel
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Correspondence to Lorraine V. Kalia.

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Conflict of Interest

Kaie Rosborough and Neha Patel declare that they have no conflict of interest.

Lorraine V. Kalia holds a Canadian Health Institutes of Research (CIHR) Clinician-Scientist Award; receives research support from the Natural Sciences and Engineering Research Council of Canada (NSERC), Michael J. Fox Foundation for Parkinson’s Research, J. P. Bickell Foundation, University of Toronto Centre for Collaborative Drug Research, and Toronto General & Western Hospital Foundation; and received research support from Parkinson’s UK and educational support from Allergan.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Movement Disorders

The editors would like to thank Dr. John Brust for taking the time to review this manuscript.

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Rosborough, K., Patel, N. & Kalia, L.V. α-Synuclein and Parkinsonism: Updates and Future Perspectives. Curr Neurol Neurosci Rep 17, 31 (2017). https://doi.org/10.1007/s11910-017-0737-y

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