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Review
. 2014 Dec;23(4):292-313.
doi: 10.5607/en.2014.23.4.292. Epub 2014 Dec 12.

Alpha-synuclein function and dysfunction on cellular membranes

David Snead  1 , David Eliezer  1
Affiliations
Review

Alpha-synuclein function and dysfunction on cellular membranes

David Snead et al. Exp Neurobiol. 2014 Dec.

Abstract

Alpha-synuclein is a small neuronal protein that is closely associated with the etiology of Parkinson's disease. Mutations in and alterations in expression levels of alpha-synuclein cause autosomal dominant early onset heredity forms of Parkinson's disease, and sporadic Parkinson's disease is defined in part by the presence of Lewy bodies and Lewy neurites that are composed primarily of alpha-synuclein deposited in an aggregated amyloid fibril state. The normal function of alpha-synuclein is poorly understood, and the precise mechanisms by which it leads to toxicity and cell death are also unclear. Although alpha-synuclein is a highly soluble, cytoplasmic protein, it binds to a variety of cellular membranes of different properties and compositions. These interactions are considered critical for at least some normal functions of alpha-synuclein, and may well play critical roles in both the aggregation of the protein and its mechanisms of toxicity. Here we review the known features of alpha-synuclein membrane interactions in the context of both the putative functions of the protein and of its pathological roles in disease.

Keywords: Parkinson; aggregation; alpha-synuclein; amyloid; neurotransmission; synucleinopathy.

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Figures

Fig. 1
Fig. 1
Cellular membranes, targets and pathways potentially involved in the normal, physiological functions of alpha-synuclein.
Fig. 2
Fig. 2
Cellular membranes, targets and pathways potentially involved in alpha-synuclein dysfunction and its role in disease states in the synucleinopathies.
See this image and copyright information in PMC

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References

    1. Pfefferkorn CM, Jiang Z, Lee JC. Biophysics of α-synuclein membrane interactions. Biochim Biophys Acta. 2012;1818:162–171. - PMC - PubMed
    1. Dikiy I, Eliezer D. Folding and misfolding of alpha-synuclein on membranes. Biochim Biophys Acta. 2012;1818:1013–1018. - PMC - PubMed
    1. Spillantini MG. Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are α-synucleinopathies. Parkinsonism Relat Disord. 1999;5:157–162. - PubMed
    1. Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson's disease. Annu Rev Neurosci. 2005;28:57–87. - PubMed
    1. Luk KC, Lee VM. Modeling Lewy pathology propagation in Parkinson's disease. Parkinsonism Relat Disord. 2014;20(Suppl 1):S85–S87. - PMC - PubMed