Perry, George

Publication Detail

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P38 activation mediates amyloid-beta cytotoxicity.

Xiongwei Zhu; Matthew Mei; Hyoung-Gon Lee; Yang Wang; Jiahuai Han; George Perry; Mark A Smith (Profiled Authors: Smith, Mark A; Zhu, Xiongwei; Perry, George)

Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, Ohio 44106, USA. Xiongwei.Zhu@case.edu
Neurochemical research 2005;30(6-7):791-6.

Amyloid-beta is a leading candidate factor in the development of Alzheimer disease (AD), however the mechanisms involved are unclear. As such, there has been considerable interest in evidence showing that the neuronal damage caused by amyloid-beta is mediated by oxidative stress. Notably, oxidative stress leads to activation of stress-activated protein kinases, which we and others have shown are also involved in AD pathogenesis. One SAPK in particular, p38, appears to be crucial in AD and therefore, in the current study, we investigated the role of p38 activation in amyloid-beta cytotoxicity. Our data showed p38 activation was induced by amyloid-beta in a concentration-dependent manner in M17 human neuroblastoma cells. Notably, amyloid-beta toxicity was significantly decreased by inhibition of p38 activity by overexpressing dominant negative p38. Consistent with this, in primary cortical neurons amyloid-beta also induced p38 activation and amyloid-beta toxicity was significantly diminished when p38 was inhibited by its specific inhibitor, SB203580. Taken together, these data suggest that p38 is a key downstream effector of amyloid-beta-induced neuronal death and blocking this pathway may be of therapeutic value.

1 Originating Grant

• 1.

  Smith, Mark A

  METABOLIC ABNORMALITIES IN ALZHEIMER DISEASE

  1 May 1999 - 30 April 2006

  NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

  Total Funding: $ 750,386

Scientific Context

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