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Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein.

alpha-Synucleinopathies are neurodegenerative disorders that range pathologically from the demise of select groups of nuclei to pervasive degeneration throughout the neuraxis. Although mounting evidence suggests that alpha-synuclein lesions lead to neurodegeneration, this remains controversial. To explore this issue, we generated transgenic mice expressing wild-type and A53T human alpha-synuclein in CNS neurons. Mice expressing mutant, but not wild-type, alpha-synuclein developed a severe and complex motor impairment leading to paralysis and death. These animals developed age-dependent intracytoplasmic neuronal alpha-synuclein inclusions paralleling disease onset, and the alpha-synuclein inclusions recapitulated features of human counterparts. Moreover, immunoelectron microscopy revealed that the alpha-synuclein inclusions contained 10-16 nm wide fibrils similar to human pathological inclusions. These mice demonstrate that A53T alpha-synuclein leads to the formation of toxic filamentous alpha-synuclein neuronal inclusions that cause neurodegeneration.

Pubmed ID: 12062037


  • Giasson BI
  • Duda JE
  • Quinn SM
  • Zhang B
  • Trojanowski JQ
  • Lee VM



Publication Data

May 16, 2002

Associated Grants


Mesh Terms

  • Animals
  • Axons
  • Behavior, Animal
  • Brain
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Humans
  • Inclusion Bodies
  • Male
  • Mice
  • Mice, Transgenic
  • Microscopy, Electron
  • Movement Disorders
  • Nerve Tissue Proteins
  • Neurodegenerative Diseases
  • Neurons
  • Phenotype
  • Recombinant Fusion Proteins
  • Solubility
  • Spinal Cord
  • Synucleins
  • Wallerian Degeneration
  • alpha-Synuclein