期刊
EXPERIMENTAL NEUROLOGY
卷 187, 期 2, 页码 279-288出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2004.01.007
关键词
neurodegenerative disease; Parkinson's disease; Alzheimer's disease; Lewy body; alpha-synuclein; synucleinopathies; microtubule-associated protein tau; tauopathies; fibrillization; amyloid
Mutations in the alpha-synuclein (alpha-syn) gene are responsible for a rare familial parkinsonism syndrome, a finding that has led to extensive characterization of altered alpha-syn structure in sporadic Parkinson's disease (PD) and other neurodegenerative disorders. We report here the immunohistochemical, biochemical and ultrastructural characterization of alpha-syn neuropathology in a case of familial PD with the A53T alpha-syn gene mutation. Insoluble filamentous alpha-syn lesions were detected in almost all brain regions examined and as in sporadic PD, we observed the accumulation of insoluble nitrated alpha-syn in this familial disorder. Significant accumulations of filamentous insoluble tau protein also were detected in some brain regions of this patient, suggesting a role for A53T mutant alpha-syn in tau fibrillization. Indeed, in vitro studies of tau and alpha-syn fibrillization showed that the A53T mutation accelerated alpha-syn fibril formation, initiated tau assembly into filaments and synergistically enhanced fibrillization of both tau and alpha-syn. Our data implicate fibrillization of alpha-syn and tau in the pathogenesis of PD, and suggest that distinct amyloidogenic proteins may cross-seed each other in neurodegenerative diseases. (C) 2004 Elsevier Inc. All rights reserved.
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