KMID : 0892920110200020067
|
|
Experimental Neurobiology 2011 Volume.20 No. 2 p.67 ~ p.80
|
|
The Interface between Cytoskeletal Aberrations and Mitochondrial Dysfunction in Alzheimer¡¯s Disease and Related Disorders
|
|
Kang David E.
Roh Seung-Eon Woo Jung-A Liu Tian Bu Jung-Hyun Jung A-Rong Lim Yeo-Ry
|
|
Abstract
|
|
|
The major defining pathological hallmarks of Alzheimer¡¯s disease (AD) are the accumulations of A¥â in senile plaques and hyperphosphorylated tau in neurofibrillary tangles and neuropil threads. Recent studies indicate that rather than these insoluble lesions, the soluble A¥â 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 A¥â to various integrins, defects in downstream focal adhesion signaling, and activation of cofilin can impact mitochondrial dysfunction, cytoskeletal changes, and tau pathology induced by A¥â oligomers. Such pathological consequences can also feedback to further activate cofilin to promote cofilin pathology. We also suggest that the mechanism of A¥â generation by the endocytosis of APP is mechanistically linked with perturbations in integrin-based focal adhesion signaling, as APP, LRP, and ¥â-integrins are physically associated with each other.
|
|
KEYWORD
|
|
integrin, focal adhesion, cofilin, amyloid, mitochondria, cytoskeleton
|
|
FullTexts / Linksout information
|
|
|
|
Listed journal information
|
|
|
|