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Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release.

ABSTRACT: In Alzheimer's disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (A?) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic A? of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 family protein BAK is suppressed by siRNA, A? oligomer-induced cell death was reduced. Furthermore, significant reduction of cytochrome c release was observed with mitochondria isolated from BAK siRNA-treated HT-22 cells. Our in vitro experiments demonstrate that A? oligomers bind to BAK on the membrane and induce apoptotic BAK pores and cytochrome c release. Thus, the results suggest that A? oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death.

SUBMITTER: Kim J

PROVIDER: S-EPMC4190645 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Beta-amyloid oligomers activate apoptotic BAK pore for cytochrome c release.

Kim Jaewook J Yang Yoosoo Y Song Seung Soo SS Na Jung-Hyun JH Oh Kyoung Joon KJ Jeong Cherlhyun C Yu Yeon Gyu YG Shin Yeon-Kyun YK

Biophysical journal 20141001 7

In Alzheimer's disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (Aβ) oligomers are known to be the neurotoxins responsible for neuronal cell death, the underlying mechanisms remain largely elusive. Here, we report that the oligomeric form of synthetic Aβ of 42 amino acids elicits death of HT-22 cells. But, when expression of a bcl-2 family protein BAK is suppressed by siRNA, Aβ oligomer-induced cell death was reduced. Furthermore, signi ...[more]

PMID: 25296312

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