Kim, Jaewook Yang, Yoosoo Song, Seung Soo Na, Jung-Hyun Oh, Kyoung Joon Jeong, Cherlhyun Yu, Yeon Gyu Shin, Yeon-Kyun 2024-01-20T08:34:06Z 2024-01-20T08:34:06Z 2021-09-02 2014-10-07 0006-3495 https://pubs.kist.re.kr/handle/201004/126247 In Alzheimer's disease, cytochrome c-dependent apoptosis is a crucial pathway in neuronal cell death. Although beta-amyloid (A beta) 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 beta 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 beta 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 beta oligomers bind to BAK on the membrane and induce apoptotic BAK pores and cytochrome c release. Thus, the results suggest that A beta oligomers function as apoptotic ligands and hijack the intrinsic apoptotic pathway to cause unintended neuronal cell death. English CELL PRESS BCL-2 FAMILY-MEMBER ALZHEIMERS-DISEASE CELL-DEATH CONFORMATIONAL-CHANGES MECHANISMS NEURODEGENERATION MITOCHONDRIA PROTEINS BINDING Beta-Amyloid Oligomers Activate Apoptotic BAK Pore for Cytochrome c Release Article 10.1016/j.bpj.2014.07.074 1 BIOPHYSICAL JOURNAL, v.107, no.7, pp.1601 - 1608 BIOPHYSICAL JOURNAL 107 7 1601 1608 scie scopus 000342880700015 2-s2.0-84908202877 Biophysics Biophysics Article BCL-2 FAMILY-MEMBER ALZHEIMERS-DISEASE CELL-DEATH CONFORMATIONAL-CHANGES MECHANISMS NEURODEGENERATION MITOCHONDRIA PROTEINS BINDING apoptosis BAK beta-amyloid cytochrome c release