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P3‐221: Dynein dysfunction causes the disturbance of synaptic vesicle transport and axonal swelling
Author(s) -
Kimura Nobuyuki,
Okabayashi Sachi,
Ono Fumiko
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1663
Subject(s) - dynactin , dynein , axoplasmic transport , microbiology and biotechnology , endocytic cycle , microtubule , synaptic vesicle , vesicular transport protein , biology , endosome , neurotransmission , neuroscience , chemistry , vesicle , endocytosis , intracellular , biochemistry , receptor , membrane
Background: Cytoplasmic dynein, a microtubule-based motorprotein, interacts with another microtubule-associated protein, dynactin. The resulting dynein-dynactin complex mediates minus end-directed vesicle transport, including endosome trafficking. We have previously shown that dynein-mediated transport is impaired in aged-monkey brains, and we demonstrated that dynein dysfunction causes intracellular Aß accumulation via endocytic dysfunction. However, it remains unclear whether dynein dysfunction is directly involved in the process of age-related cognitive dysfunction. Methods: We carried on both RNA interference study and drug treatment study to clarify whether dynein dysfunction affects neurotransmission, such as neurotrophic factor signal and synaptic vesicle transport. Results: Here, we demonstrated that siRNA-induced dynein dysfunction disturbed the retrograde transport of TrkB receptor via endocyticdysfuntion. Moreover, it also resulted in the disturbance of synaptic vesicle transport and axonal swelling. In such swollen neurites, neurofilament was significantly accumulated. Conclusions: These findings suggest that dynein dysfunction itself can cause the disturbance of neurotransmission independently of Aß toxicity. Taken together, dynein dysfunction may be one of the causative risk factors for sporadic Alzheimer’s disease.