Exp Neurobiol 2011; 20(2): 67-80
Published online June 30, 2011
© The Korean Society for Brain and Neural Sciences
David E. Kang1,2*, Seung Eon Roh2, Jung A Woo2, Tian Liu2, Jung Hyun Bu1, A-Rong Jung2 and Yeory Lim2
1Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA, 2WCU-Neurocytomics Program, Seoul National University College of Medicine, Seoul 110-799, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 858-822-6484, FAX: 858-822-1021
The major defining pathological hallmarks of Alzheimer's disease (AD) are the accumulations of Aβ in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble Aβ oligomers and hyperphosphorylated tau are the toxic agents of AD pathology. Such pathological protein species are accompanied by cytoskeletal changes, mitochondrial dysfunction, Ca2+ dysregulation, and oxidative stress. In this review, we discuss how the binding of Aβ to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by Aβ oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of Aβ generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and β-integrins are physically associated with each other.
Keywords: integrin, focal adhesion, cofilin, amyloid, mitochondria, cytoskeleton