Apoptosis in health and disease and modulation of apoptosis for therapy: An overview |
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| Authors: | Neeta Singh |
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| Institution: | (1) Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, 110029 New Delhi |
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| Abstract: | Apoptosis a physiological mechanism that eliminates excessive, damaged or unwanted cells, is a highly regulated pathway important
for maintaining homeostasis in multicellular organisms. It can be initiated through various signals via the extrinsic pathway
which involves death receptors, or via the intrinsic pathway which is initiated by intracellular damage and involves the mitochondria
and release of cytochrome c from it to further activate caspases. The Bcl-2 family of proteins is situated upstream to the
irreversible damage of cellular constituents and is an important checkpoint in the fate of a cell. The pro-apoptotic members,
BH3 only members include BID, BAD and BIM. They directly or indirectly activate multidomain BAX/BAK that constitute the requisite
gateway to the intrinsic pathway which operates at the mitochondrial surface and endoplasmic reticulum. In contrast, antiapoptotic
members such as Bcl-2, Bcl-XL bind and sequester activation. Downstream of mitochondria, the apoptosome involvement is seen
to generate caspase activity. Post mitochondria regulation involves IAPs, and their inhibitors. The pathogenesis of several
diseases such as cancer, neurodegenerative disorders, autoimmune disorders, heart disease, infectious diseases including AIDS
is closely related to aberrant apoptosis. Consequently interest has emerged in employing various the rapeutic approaches such
as gene therapy, antisense therapy, recombinant biologicals, organic and combinatorial chemistry, to specifically target apoptosis
signaling pathways such as death receptors FAS/TRAIL, Bcl-2, p53, IAPs, SMAC and caspases, etc. and are now advancing from
preclinical to clinical phase. |
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| Keywords: | Apoptosis Mitochondria Caspases Death receptors Apoptosis based therapies |
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