Neuropathology, biochemistry, and biophysics of α-synuclein aggregation

Authors

  • Vladimir N. Uversky

    1. Department of Biochemistry and Molecular Biology, Center for Computational Biology and Bioinformatics, Indiana University School of Medicine, Indianapolis, Indiana, USA
    2. Institute for Biological Instrumentation, Russian Academy of Sciences, Moscow, Russia
    Search for more papers by this author

Address correspondence and reprint requests to Vladimir N. Uversky, DSc, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS#4021, Indianapolis, IN 46202, USA. E-mail: vuversky@iupui.edu

Abstract

Aggregation of α-synuclein, an abundant and conserved pre-synaptic brain protein, is implicated as a critical factor in several neurodegenerative diseases. These diseases, known as synucleinopathies, include Parkinson’s disease, dementia with Lewy bodies (LBs), diffuse LB disease, the LB variant of Alzheimer’s disease, multiple system atrophy, and neurodegeneration with brain iron accumulation type I. Although the precise nature of in vivoα-synuclein function remains elusive, considerable knowledge has been accumulated about its structural properties and conformational behavior. α-Synuclein is a typical natively unfolded protein. It is characterized by the lack of rigid, well-defined, 3-D structure and possesses remarkable conformational plasticity. The structure of this protein depends dramatically on its environment and it accommodates a number of unrelated conformations. This paper provides an overview of the biochemistry, biophysics, and neuropathology of α-synuclein aggregation.

Ancillary