Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Clin Invest. 2002 Nov;110(10):1429-39.

Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies.

Author information

  • 1Department of Neuropathology, Ludwig Maximilians University, Munich, Germany.

Abstract

The pathological modifications of alpha-synuclein (alphaS) in Parkinson disease and related diseases are poorly understood. We have detected misfolded alphaS in situ based on the proteinase K resistance (PK resistance) of alphaS fibrils, and using specific antibodies against S129-phosphorylated alphaS as well as oxidized alphaS. Unexpectedly massive neuritic pathology was found in affected human brain regions, in addition to classical alphaS pathology. PK resistance and abnormal phosphorylation of alphaS developed with increasing age in (Thy1)-h[A30P] alphaS transgenic mice, concomitant with formation of argyrophilic, thioflavin S-positive, and electron-dense inclusions that were occasionally ubiquitinated. alphaS pathology in the transgenic mice was predominantly in the brainstem and spinal cord. Astrogliosis was found in these heavily affected tissues. Homozygous mice showed the same pathology approximately one year earlier. The transgenic mice showed a progressive deterioration of locomotor function. Thus, misfolding and hyperphosphorylation of alphaS may cause dysfunction of affected brain regions.

PMID:
12438441
[PubMed - indexed for MEDLINE]
PMCID:
PMC151810
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Journal of Clinical Investigation Icon for PubMed Central
    Loading ...
    Write to the Help Desk