• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Pathological changes in dopaminergic nerve cells of the substantia nigra and olfactory bulb in mice transgenic for truncated human alpha-synuclein(1-120): implications for Lewy body disorders.

Dysfunction of the 140 aa protein alpha-synuclein plays a central role in Lewy body disorders, including Parkinson's disease, as well as in multiple system atrophy. Here, we show that the expression of truncated human alpha-synuclein(1-120), driven by the rat tyrosine hydroxylase promoter on a mouse alpha-synuclein null background, leads to the formation of pathological inclusions in the substantia nigra and olfactory bulb and to a reduction in striatal dopamine levels. At the behavioral level, the transgenic mice showed a progressive reduction in spontaneous locomotion and an increased response to amphetamine. These findings suggest that the C-terminal of alpha-synuclein is an important regulator of aggregation in vivo and will help to understand the mechanisms underlying the pathogenesis of Lewy body disorders and multiple system atrophy.

Pubmed ID: 16611810

Authors

  • Tofaris GK
  • Garcia Reitböck P
  • Humby T
  • Lambourne SL
  • O'Connell M
  • Ghetti B
  • Gossage H
  • Emson PC
  • Wilkinson LS
  • Goedert M
  • Spillantini MG

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

April 12, 2006

Associated Grants

  • Agency: Parkinson's UK, Id: G-4039
  • Agency: Medical Research Council, Id: MC_U105184291
  • Agency: NIA NIH HHS, Id: P30 AG10133

Mesh Terms

  • Animals
  • Dopamine
  • Humans
  • Lewy Bodies
  • Lewy Body Disease
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Neurons
  • Olfactory Bulb
  • Parkinson Disease
  • Promoter Regions, Genetic
  • Rats
  • Substantia Nigra
  • Tyrosine 3-Monooxygenase
  • alpha-Synuclein