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June 10, 2023

Apoptosis: From Molecular Pathways to Clinical Implications

# Apoptosis Physiology and Pathology ## Introduction - What is apoptosis and why is it important for normal health and disease - How apoptosis is regulated by different pathways and proteins - What are the main types of apoptosis: extrinsic and intrinsic - What are the morphological and biochemical features of apoptotic cells ## Extrinsic Apoptosis Pathway - How extrinsic apoptosis is triggered by death receptors on the cell surface - How death receptors activate caspase-8 and caspase-10, which initiate the execution of apoptosis - How some cells can resist extrinsic apoptosis by expressing anti-apoptotic proteins such as FLIP or BCL-2 - What are the physiological and pathological roles of extrinsic apoptosis in immune system, development and cancer ## Intrinsic Apoptosis Pathway - How intrinsic apoptosis is triggered by various intracellular stresses such as DNA damage, oxidative stress or growth factor withdrawal - How intrinsic apoptosis is regulated by the balance between pro-apoptotic and anti-apoptotic BCL-2 family proteins - How pro-apoptotic BCL-2 proteins induce mitochondrial outer membrane permeabilization (MOMP), which releases cytochrome c and other apoptogenic factors into the cytosol - How cytochrome c binds to Apaf-1 and forms the apoptosome, which activates caspase-9, which in turn activates caspase-3 and caspase-7 - What are the physiological and pathological roles of intrinsic apoptosis in development, neurodegeneration, cancer and ischemia ## Apoptosis Execution Phase - How caspase-3 and caspase-7 cleave various substrates that lead to the characteristic changes of apoptotic cells - How caspase-6 contributes to nuclear fragmentation and chromatin condensation - How caspase-activated DNase (CAD) causes DNA fragmentation into oligonucleosomal units - How apoptotic cells expose phosphatidylserine on their outer membrane, which signals their removal by phagocytes - How apoptotic cells release cytokines and chemokines that modulate inflammation and tissue repair ## Apoptosis Dysregulation and Disease - How too much or too little apoptosis can cause various diseases such as cancer, autoimmune disorders, neurodegenerative diseases and viral infections - How mutations or alterations in apoptotic genes or proteins can affect the susceptibility or resistance to apoptosis - How therapeutic strategies can target apoptosis to enhance or inhibit cell death in different diseases - How novel biomarkers can be used to monitor apoptosis in vivo ## Conclusion - Summarize the main points of the article - Emphasize the importance of apoptosis for normal health and disease - Highlight the challenges and opportunities for future research on apoptosis ## FAQs - What is the difference between apoptosis and necrosis? - What are some examples of physiological apoptosis? - What are some examples of pathological apoptosis? - How can apoptosis be measured experimentally? - What are some drugs that modulate apoptosis?