- Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.
Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders.
Science (New York, N.Y.) (2000-02-26)
E Masliah, E Rockenstein, I Veinbergs, M Mallory, M Hashimoto, A Takeda, Y Sagara, A Sisk, L Mucke
PMID10678833
ABSTRACT
To elucidate the role of the synaptic protein alpha-synuclein in neurodegenerative disorders, transgenic mice expressing wild-type human alpha-synuclein were generated. Neuronal expression of human alpha-synuclein resulted in progressive accumulation of alpha-synuclein-and ubiquitin-immunoreactive inclusions in neurons in the neocortex, hippocampus, and substantia nigra. Ultrastructural analysis revealed both electron-dense intranuclear deposits and cytoplasmic inclusions. These alterations were associated with loss of dopaminergic terminals in the basal ganglia and with motor impairments. These results suggest that accumulation of wild-type alpha-synuclein may play a causal role in Parkinson's disease and related conditions.