Review: formation and properties of amyloid-like fibrils derived from alpha-synuclein and related proteins

J Struct Biol. 2000 Jun;130(2-3):300-9. doi: 10.1006/jsbi.2000.4262.

Abstract

Synucleinsare small proteins that are highly expressed in brain tissue and are localised at presynaptic terminals in neurons. alpha-Synuclein has been identified as a component of intracellular fibrillar protein deposits in several neurodegenerative diseases, and two mutant forms of alpha-synuclein have been associated with autosomal-dominant Parkinson's Disease. A fragment of alpha-synuclein has also been identified as the non-Abeta component of Alzheimer's Disease amyloid. In this review we describe some structural properties of alpha-synuclein and the two mutant forms, as well as alpha-synuclein fragments, with particular emphasis on their ability to form beta-sheet on ageing and aggregate to form amyloid-like fibrils. Differences in the rates of aggregation and morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins are highlighted. Interactions between alpha-synuclein and other proteins, especially those that are components of amyloid or Lewy bodies, are considered. The toxicity of alpha-synuclein and related peptides towards neurons is also discussing in relation to the aetiology of neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Amyloid*
  • Base Sequence
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins* / genetics
  • Nerve Tissue Proteins* / metabolism
  • Nerve Tissue Proteins* / ultrastructure
  • Neurodegenerative Diseases / metabolism
  • Protein Conformation
  • Synucleins
  • alpha-Synuclein

Substances

  • Amyloid
  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein