Current Protein & Peptide Science

Ben M. Dunn  
Department of Biochemistry and Molecular Biology University of Florida
College of Medicine, P.O. Box 100245, Gainesville
Florida, FL 32610-0245


α-Synuclein Misfolding and Neurodegenerative Diseases

Author(s): Vladimir N. Uversky

Affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 410 W. 10th Street, HS 5000, Indianapolis, IN 46202, USA.


α-Synuclein is an abundant presynaptic brain protein, misfolding, aggregation and fibrillation of which are implicated as critical factors in several neurodegenerative diseases. The list of the well-known synucleinopathies includes such devastating disorders as Parkinsons disease, Lewy body variant of Alzheimers disease, diffuse Lewy body disease, dementia with Lewy bodies, multiple system atrophy, and neurodegeneration with brain iron accumulation type I. The precise functions of α-synuclein remain elusive, but there are evidence indicating its involvement in regulation vesicular release and/or turnover and synaptic function in the central nervous system. It might play a role in neuronal plasticity responses, bind fatty acids, regulate certain enzymes, transporters, and neurotransmitter vesicles, be involved in neuronal survival and even can act as a molecular chaperone. Structurally, α-synuclein is an illustrative member of the rapidly growing family of natively unfolded (or intrinsically disordered) proteins and considerable knowledge has been accumulated about its structural properties and conformational behavior. The molecular mechanisms underlying misfolding, aggregation and fibrillation of α-synuclein and the role of various environmental and genetic factors in stimulation and inhibition of these processes are relatively well understood. Here, the main structural features of α-synuclein, its functions, and involvement in various human diseases are summarized providing a foundation for better understanding of the biochemistry, biophysics and neuropathology of α-synuclein aggregation.

Keywords: α-Synuclein, synucleinopathies, aggregation, fibril, nerodegeneration, natively unfolded protein

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Article Details

Page: [507 - 540]
Pages: 34
DOI: 10.2174/138920308785915218
Price: $58