Tags

Type your tag names separated by a space and hit enter

Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity.
Cell Death Dis 2012; 3:e309CD

Abstract

Although oligomeric β-amyloid (Aβ) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aβ induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aβ-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aβ. Here, we found that treatment with oligomeric Aβ increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aβ-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aβ-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD.

Authors+Show Affiliations

Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22592316

Citation

Kudo, W, et al. "Inhibition of Bax Protects Neuronal Cells From Oligomeric Aβ Neurotoxicity." Cell Death & Disease, vol. 3, 2012, pp. e309.
Kudo W, Lee HP, Smith MA, et al. Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity. Cell Death Dis. 2012;3:e309.
Kudo, W., Lee, H. P., Smith, M. A., Zhu, X., Matsuyama, S., & Lee, H. G. (2012). Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity. Cell Death & Disease, 3, pp. e309. doi:10.1038/cddis.2012.43.
Kudo W, et al. Inhibition of Bax Protects Neuronal Cells From Oligomeric Aβ Neurotoxicity. Cell Death Dis. 2012 May 17;3:e309. PubMed PMID: 22592316.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of Bax protects neuronal cells from oligomeric Aβ neurotoxicity. AU - Kudo,W, AU - Lee,H-P, AU - Smith,M A, AU - Zhu,X, AU - Matsuyama,S, AU - Lee,H-G, Y1 - 2012/05/17/ PY - 2012/5/18/entrez PY - 2012/5/18/pubmed PY - 2012/7/24/medline SP - e309 EP - e309 JF - Cell death & disease JO - Cell Death Dis VL - 3 N2 - Although oligomeric β-amyloid (Aβ) has been suggested to have an important role in Alzheimer disease (AD), the mechanism(s) of how Aβ induces neuronal cell death has not been fully identified. The balance of pro- and anti-apoptotic Bcl-2 family proteins (e.g., Bcl-2 and Bcl-w versus Bad, Bim and Bax) has been known to have a role in neuronal cell death and, importantly, expression levels of these proteins are reportedly altered in the vulnerable neurons in AD. However, the roles of apoptotic proteins in oligomeric Aβ-induced cell death remain unclear in vivo or in more physiologically relevant models. In addition, no study to date has examined whether Bax is required for the toxicity of oligomeric Aβ. Here, we found that treatment with oligomeric Aβ increased Bim levels but decreased Bcl-2 levels, leading to the activation of Bax and neuronal cell death in hippocampal slice culture and in vivo. Furthermore, the inhibition of Bax activity either by Bax-inhibiting peptide or bax gene knockout significantly prevented oligomeric Aβ-induced neuronal cell death. These findings are first to demonstrate that Bax has an essential role in oligomeric Aβ-induced neuronal cell death, and that the targeting of Bax may be a therapeutic approach for AD. SN - 2041-4889 UR - https://www.unboundmedicine.com/medline/citation/22592316/Inhibition_of_Bax_protects_neuronal_cells_from_oligomeric_Aβ_neurotoxicity_ L2 - http://dx.doi.org/10.1038/cddis.2012.43 DB - PRIME DP - Unbound Medicine ER -