Axonal transport of human alpha-synuclein slows with aging but is not affected by familial Parkinson's disease-linked mutations

J Neurochem. 2004 Jan;88(2):401-10. doi: 10.1046/j.1471-4159.2003.02166.x.


Biochemical and genetic abnormalities of alpha-synuclein (alpha-Syn) are implicated in the pathogenesis of Parkinson's disease (PD) and other alpha-synucleinopathies. The abnormal intraneuronal accumulations of alpha-Syn in Lewy bodies (LBs) and Lewy neurites (LNs) have implicated defects in axonal transport of alpha-Syn in the alpha-synucleinopathies. Using human (Hu) alpha-Syn transgenic (Tg) mice, we have examined whether familial PD (FPD)-linked mutations (A30P and A53T) alter axonal transport of Hualpha-Syn. Our studies using peripheral nerves show that Hualpha-Syn and Moalpha-Syn are almost exclusively transported in the slow component (SC) of axonal transport and that the FPD-linked alpha-Syn mutations do not have obvious effects on the axonal transport of alpha-Syn. Moreover, older pre-symptomatic A53T Hualpha-Syn Tg mice do not show gross alterations in the axonal transport of alpha-Syn and other proteins in the SC, indicating that the early stages of alpha-synucleinopathy in A53T alpha-Syn Tg mice are not associated with gross alterations in the slow axonal transport. However, the axonal transport of alpha-Syn slows significantly with aging. Because the rate of axonal transport affects the stability and accumulation of proteins in axons, age-dependent-slowing alpha-Syn is a likely contributor to axonal aggregation of alpha-Syn in alpha-synucleinopathy.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Animals
  • Axonal Transport / physiology*
  • Humans
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / physiology*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Parkinsonian Disorders / genetics
  • Parkinsonian Disorders / metabolism*
  • Peripheral Nerves / metabolism
  • Synucleins
  • alpha-Synuclein


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