Tubulin seeds alpha-synuclein fibril formation

J Biol Chem. 2002 Jan 18;277(3):2112-7. doi: 10.1074/jbc.M102981200. Epub 2001 Nov 6.

Abstract

Increasing evidence suggests that alpha-synuclein is a common pathogenic molecule in several neurodegenerative diseases, particularly in Parkinson's disease. To understand alpha-synuclein pathology, we investigated molecules that interact with alpha-synuclein in human and rat brains and identified tubulin as an alpha-synuclein binding/associated protein. Tubulin co-localized with alpha-synuclein in Lewy bodies and other alpha-synuclein-positive pathological structures. Tubulin initiated and promoted alpha-synuclein fibril formation under physiological conditions in vitro. These findings suggest that an interaction between tubulin and alpha-synuclein might accelerate alpha-synuclein aggregation in diseased brains, leading to the formation of Lewy bodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • Humans
  • Microscopy, Electron
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism*
  • Neurodegenerative Diseases / metabolism
  • Rats
  • Synucleins
  • Tubulin / metabolism*
  • alpha-Synuclein

Substances

  • Nerve Tissue Proteins
  • SNCA protein, human
  • Snca protein, rat
  • Synucleins
  • Tubulin
  • alpha-Synuclein