Exp Neurobiol 2006; 15(1): 7-13
Published online July 1, 2006
© The Korean Society for Brain and Neural Sciences
SeungYong Yoon, JungEun Choi and DongHou Kim*
Department of Anatomy and Cell Biology and Research Institute for Biomacromolecules, University of Ulsan College of Medicine, Seoul 138-736, *Department of Anatomy and Cell Biology, University of Ulsan College of Medicine, Seoul 138-736, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-2-3010-4272, FAX: 82-2-3010-4240
Hyperphosphorylation of tau is a characteristic feature of the neurodegenerative pathology in Alzheimer's disease (AD), and glycogen synthase kinase-3Ղ (GSK-3Ղ) and the cdk5/p35 system are thought to play important roles in tau hyperphosphorylation. Okadaic acid, which increases tau phosphorylation and neuronal death, has been used as a research model of AD. We previously showed that GSK-3Ղ was inactivated during okadaic acid-induced neurodegeneration. To extend this observation, we have assayed the involvement of the p35/cdk5 system in okadaic acid-induced neurodegeneration. We observed a significant increase in p35 cleavage during okadaic acid-induced neuron degeneration, indicative of cdk5 activation. We also observed sequestration of cdk5 in the nucleus of the neuron, indicating that cdk5 may contribute to neuronal dysfunction rather than to cytoskeleton disruption in the cytosol. We also observed enhanced MPM2 immunoreactivity in the cell bodies of degenerating neurons. These findings provide evidence for the aberrant expression of mitotic cell cycle proteins during the pathogenesis of neuronal degeneration processes, such as those occurring in AD.
Keywords: Alzheimer's disease, okadaic acid, p35, Cdk5, tau phosphorylation