Demonstration of a role for alpha-synuclein as a functional microtubule-associated protein

J Alzheimers Dis. 2004 Aug;6(4):435-42; discussion 443-9. doi: 10.3233/jad-2004-6412.


Alpha-synuclein is a major constituent of pathological intracellular inclusion bodies, a common feature of several neurodegenerative diseases. Two missense mutations in the alpha-synuclein gene have been identified in confirmed autosomal-dominant familial Parkinson's disease, which segregate with the illness. However, the physiological function of alpha-synuclein remains unknown. After biochemical investigations we have revealed tubulin to be an alpha-synuclein associated/binding protein. Here, we show that alpha-synuclein induces polymerization of purified tubulin into microtubules. Mutant forms of alpha-synuclein lose this potential. The binding site of alpha-synuclein to tubulin is identified, and co-localization of alpha-synuclein with microtubules is shown in cultured cells. To our knowledge, this is the first demonstration of microtubule-polymerizing activity of alpha-synuclein. Now we can see a striking resemblance between alpha-synuclein and tau: both have the same physiological function and pathological features, making abnormal structures in diseased brains known as synucleinopathies and tauopathies. The discovery of a physiological role for alpha-synuclein may provide a new dimension in researches into the mechanisms of alpha-synuclein-associated neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases
  • Animals
  • Binding Sites
  • Brain / metabolism
  • Brain / pathology
  • COS Cells / metabolism
  • DNA Primers / genetics
  • DNA-Binding Proteins / metabolism
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology
  • Intracellular Space / metabolism
  • Intracellular Space / pathology
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • Mutation, Missense / genetics
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology*
  • Phosphoproteins / metabolism
  • Point Mutation / genetics
  • Polymerase Chain Reaction
  • Swine
  • Synucleins
  • Transfection / methods
  • alpha-Synuclein
  • tau Proteins / metabolism


  • DNA Primers
  • DNA-Binding Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Synucleins
  • alpha-Synuclein
  • tau Proteins
  • Alcohol Oxidoreductases
  • C-terminal binding protein