Artikel ; Online: Physiological and pharmacological modulation of BAX.
Trends in pharmacological sciences
2021 Band 43, Heft 3, Seite(n) 206–220
Abstract: 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, ... ...
Abstract | 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. |
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Mesh-Begriff(e) | Apoptosis/physiology ; Humans ; Mitochondria/metabolism ; Mitochondrial Membranes/metabolism ; Proto-Oncogene Proteins c-bcl-2/metabolism ; bcl-2-Associated X Protein/metabolism |
Chemische Substanzen | Proto-Oncogene Proteins c-bcl-2 ; bcl-2-Associated X Protein |
Sprache | Englisch |
Erscheinungsdatum | 2021-11-27 |
Erscheinungsland | England |
Dokumenttyp | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review |
ZDB-ID | 282846-7 |
ISSN | 1873-3735 ; 0165-6147 |
ISSN (online) | 1873-3735 |
ISSN | 0165-6147 |
DOI | 10.1016/j.tips.2021.11.001 |
Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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