Skip NavigationSkip to Content
Return Return to Search Results

Human alpha-synuclein-harboring familial Parkinson's disease- linked Ala-53 -> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice

  1. Author:
    Lee, M. K.
    Stirling, W.
    Xu, Y. Q.
    Xu, X. Y.
    Qui, D.
    Mandir, A. S.
    Dawson, T. M.
    Copeland, N. G.
    Jenkins, N. A.
    Price, D. L.

  2. Author Address

    Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA Johns Hopkins Univ, Sch Med, Johns Hopkins Udall Parkinsons Dis Res Ctr, Baltimore, MD 21205 USA NCI, Frederick Canc Res & Dev Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA Lee MK Johns Hopkins Univ, Sch Med, Dept Pathol Neuropathol, 558 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA
    1. Year: 2002
  2. Journal: Proceedings of the National Academy of Sciences of the United States of America
    1. 99
    2. 13
    3. Pages: 8968-8973
  4. Type of Article: Article
  1. Abstract:

    Mutations in alpha-synuclein (alpha-Syn) cause Parkinson's disease (PD) in a small number of pedigrees with familial PD. Moreover, alpha-Syn accumulates as a major component of Lewy bodies and Lewy neurites, intraneuronal inclusions that are neuropathological hallmarks of PD. To better understand the pathogenic relationship between alterations in the biology of alpha-Syn and PD-associated neurodegeneration, we generated multiple lines of transgenic mice expressing high levels of either wild-type or familial PD-linked Ala-30 --> Pro (A30P) or Ala-53 --> Thr (A53T) human alpha-Syns. The mice expressing the A53T human alpha-Syn, but not wild-type or the A30P variants, develop adult-onset neurodegenerative disease with a progressive motoric dysfunction leading to death. Pathologically, affected mice exhibit neuronal abnormalities (in perikarya and neurites) including pathological accumulations of alpha-Syn and ubiquitin. Consistent with abnormal neuronal accumulation of alpha-Syn, brain regions with pathology exhibit increases in detergent-insoluble alpha-Syn and alpha-Syn aggregates. Our results demonstrate that the A53T mutant alpha-Syn causes significantly greater in vivo neurotoxicity as compared with other alpha-Syn variants. Further, alpha-Syn-dependent neurodegeneration is associated with abnormal accumulation of detergent-insoluble alpha-Syn.

    See More

  1. Keywords:

External Sources

  1. No sources found.

Library Notes

  1. No notes added.
NCI at Frederick

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel