Linking alpha-synuclein properties with oxidation: a hypothesis on a mechanism underling cellular aggregation

J Bioenerg Biomembr. 2014 Apr;46(2):93-8. doi: 10.1007/s10863-014-9540-5. Epub 2014 Jan 29.

Abstract

α-Synuclein is a small, natively unstructured protein with propensity to aggregate. α-Synuclein fibrils are major components of Lewy bodies that are hallmarks of many neurodegenerative diseases. The solution properties and aggregation behavior of α-synuclein has been well characterized, but despite numerous studies that address the role of α-synuclein in cells, a clear physiological function of this protein remains a mystery. Over a hundred review articles of α-synuclein have been written in the last decade, making it difficult to list all of the important studies that have added to our insight of α-synuclein physiology. Instead, we briefly review the status of α-synuclein research and propose a model based on the idea that α-synuclein may not have an intrinsic activity in cells but rather, it modifies the function of a group of protein partners that in turn affect cell processes. We propose that it is the loss of its cellular partners under oxidative conditions that promotes α-synuclein aggregation accelerating neuronal death.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Humans
  • Nerve Tissue Proteins / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Type C Phospholipases / metabolism*
  • alpha-Synuclein / metabolism*

Substances

  • Nerve Tissue Proteins
  • alpha-Synuclein
  • Type C Phospholipases