Physiological and pharmacological modulation of BAX

被引：153

作者：

Spitz, Adam Z. ^{[1
,2
,3
,4
,5
]}

Gavathiotis, Evripidis ^{[1
,2
,3
,4
,5
]}

机构：

[1] Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10467 USA

[2] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA

[3] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA

[4] Albert Einstein Coll Med, Wilf Family Cardiovasc Res Inst, Bronx, NY 10467 USA

[5] Albert Einstein Coll Med, Inst Aging Res, Bronx, NY 10467 USA

来源：

TRENDS IN PHARMACOLOGICAL SCIENCES | 2022年 / 43卷 / 03期

关键词：

PRO-APOPTOTIC BAX; CELL-DEATH; BCL-2; FAMILY; MEDIATED APOPTOSIS; DIRECT ACTIVATION; STRUCTURAL MODEL; PEPTIDE COMPLEX; CYTOCHROME-C; PROTEIN BAX; BINDING;

D O I：

10.1016/j.tips.2021.11.001

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Bcl-2-associated X protein (BAX) is a critical executioner of mitochondrial regulated cell death through its lethal activity of permeabilizing the mitochondrial outer membrane (MOM). While the physiological function of BAX ensures tissue homeostasis, dysregulation of BAX leads to aberrant cell death. Despite BAX being a promising therapeutic target for human diseases, historically the development of drugs has focused on antiapoptotic BCL-2 proteins, due to challenges in elucidating the mechanism of BAX activation and identifying druggable surfaces of BAX. Here, we discuss recent studies that have provided structure-function insights and identified regulatory surfaces that control BAX activation. Moreover, we emphasize the development of small molecule orthosteric, allosteric, and oligomerization modulators that provide novel opportunities for biological investigation and progress towards drugging BAX.

引用

页码：206 / 220

页数：15

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