Mechanisms and applications of apoptosis based and molecular
1. Dr Satyabrata Sahoo
DM Clinical Pharmacology Resident
Dept of Clinical & Experimental Pharmacology, CSTM
Kolkata
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2. Introduction
Apoptosis- Programmed cell death
Orderly and efficient removal of damaged cells following DNA damage
or during development
Very complex and involves many signaling pathways
Triggered through caspase-mediated intrinsic and extrinsic pathways
Balance between Pro apoptotic and anti apoptotic regulators important
key point in apoptosis.
The dysregulation of apoptosis is a symptom in a wide variety of
diseases.
Accelerated apoptosis is found in infertility, immunodeficiency, and
acute and chronic degenerative diseases
Delayed or inhibited apoptosis is present in cancer and autoimmunity
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18. Summary
Apoptosis is a cellular procedure regulated by diverse groups
of regulatory molecules in which activation of caspase plays a
crucial role.
Depending on the molecular target, different strategies are
being employed.
Fundamental features of human cancers is evasion of
apoptosis.
Leading to tumor progression and resistance to cancer
treatment.
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19. Cont..
Biologicals including death ligands or agonistic and
antagonistic antibodies that inhibit or trigger death receptor
signaling have proven efficacy in various animal models.
Among all the apoptosis-based drug targets, strategies that
target caspases are at the forefront for blocking apoptosis in
numerous diseases.
Proof-of-concept data have been obtained in several
experimental models revealing that blockade of apoptosis by
means of caspase inhibitors is a validated therapeutic
strategy
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20. Cont..
many compounds developed to modulate apoptosis are only
micromolar inhibitors.
Small-molecule drugs or peptides like caspase inhibitors have
to be optimized to readily penetrate the cells.
Drugs that selectively target different components of
apoptosis are in clinical trials
Combination of these novel agents with traditional
chemotherapy seems to be well tolerated and benefit for
patients.
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21. References
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