Apoptotic Pathways and Alzheimer’s Disease: Probing Therapeutic Potential

Apoptosis is an intrinsic biochemical, cellular process that regulates cell death and is crucial for cell survival, cellular homeostasis, and maintaining the optimum functional status. Apoptosis in a predetermined and programmed manner regulates several molecular events, including cell turnover, emb...

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Bibliographic Details
Published in:Neurochemical research 2021-12, Vol.46 (12), p.3103-3122
Main Authors: Sharma, Vivek Kumar, Singh, Thakur Gurjeet, Singh, Shareen, Garg, Nikhil, Dhiman, Sonia
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Alzheimer Disease - drug therapy
Alzheimer Disease - metabolism
Alzheimer Disease - pathology
Alzheimer's disease
Animals
Apoptosis
Apoptosis Regulatory Proteins - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell death
Cell survival
Cerebral cortex
Dementia disorders
Embryogenesis
Embryonic growth stage
Endoplasmic reticulum
Excitotoxicity
FADD protein
Homeostasis
Humans
Immune system
MAP kinase
Mitochondria
Neurochemistry
Neurodegenerative diseases
Neurology
Neuroprotective Agents - pharmacology
Neurosciences
Organelles
Oxidative stress
Plaques
Review
Signal transduction
Survival
Tau protein
TOR protein
Trophic factors
Tumor necrosis factor-α
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Summary:Apoptosis is an intrinsic biochemical, cellular process that regulates cell death and is crucial for cell survival, cellular homeostasis, and maintaining the optimum functional status. Apoptosis in a predetermined and programmed manner regulates several molecular events, including cell turnover, embryonic development, and immune system functions but may be the exclusive contributor to several disorders, including neurodegenerative manifestations, when it functions in an aberrant and disorganized manner. Alzheimer’s disease (AD) is a fatal, chronic neurodegenerative disorder where apoptosis has a compelling and divergent role. The well-characterized pathological features of AD, including extracellular plaques of amyloid-beta, intracellular hyperphosphorylated tangles of tau protein (NFTs), inflammation, mitochondrial dysfunction, oxidative stress, and excitotoxic cell death, also instigate an abnormal apoptotic cascade in susceptible brain regions (cerebral cortex, hippocampus). The apoptotic players in these regions affect cellular organelles (mitochondria and endoplasmic reticulum), interact with trophic factors, and several pathways, including PI3K/AKT, JNK, MAPK, mTOR signalling. This dysregulated apoptotic cascade end with an abnormal neuronal loss which is a primary event that may precede the other events of AD progression and correlates well with the degree of dementia. The present review provides insight into the diverse and versatile apoptotic mechanisms that are indispensable for neuronal survival and constitute an integral part of the pathological progression of AD. Identification of potential targets (restoring apoptotic and antiapoptotic balance, caspases, TRADD, RIPK1, FADD, TNFα, etc.) may be valuable and advantageous to decide the fate of neurons and to develop potential therapeutics for treatment of AD.
ISSN:0364-3190
1573-6903
DOI:10.1007/s11064-021-03418-7