Journal ArticleDOI
Apoptotic Pathways and Alzheimer's Disease: Probing Therapeutic Potential.
Vivek Kumar Sharma,Vivek Kumar Sharma,Thakur Gurjeet Singh,Shareen Singh,Nikhil Garg,Sonia Dhiman +5 more
TLDR
A review of diverse and versatile apoptotic mechanisms that are indispensable for neuronal survival and constitute an integral part of the pathological progression of Alzheimer's disease can be found in this paper, where the authors identify potential targets (restoring apoptotic and antiapoptotic balance, caspases, TRADD, RIPK1, FADD, TNFα, etc.) to decide the fate of neurons and to develop potential therapeutics for treatment of AD.Abstract:
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.read more
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TNF-mediated neuroinflammation is linked to neuronal necroptosis in Alzheimer's disease hippocampus.
Anusha Jayaraman,Thein Than Htike,Rachel James,Carmen Picón,Richard Reynolds,Richard Reynolds +5 more
TL;DR: In this paper, the authors demonstrate an increase in expression of multiple proteins in the TNF/TNF receptor-1-mediated necroptosis pathway in the AD post-mortem brain, as indicated by the phosphorylation of RIPK3 and MLKL, predominantly observed in the CA1 pyramidal neurons.
Journal ArticleDOI
Iron Dyshomeostasis and Ferroptosis: A New Alzheimer’s Disease Hypothesis?
TL;DR: The review explored the deep connection between iron dysregulation and AD pathogenesis, discussed the potential of new hypothesis related to iron dyshomeostasis and ferroptosis, and summarized the therapeutics capable of targeting iron, with the expectation to draw more attention of iron Dysregulation and corresponding drug development.
Journal ArticleDOI
New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease.
Jiao Wu,Yu Yang,Yang Wan,Jia Xia,Jin-feng Xu,Li Zhang,Yongmei Liu,Lu Chen,Fei Tang,Huifang Ao,Cheng Peng +10 more
TL;DR: In this article , a comprehensive review of the effects and underlying mechanisms of ginsenoside Rg1 on AD has been provided, which shed light on the future directions in the utilization and development of anti-AD drugs.
Journal ArticleDOI
Kynurenine Metabolism and Alzheimer’s Disease: The Potential Targets and Approaches
TL;DR: Pharmacological modulation of KP pathways has shown encouraging results, indicating that it may be a viable and explorable target for the therapy of AD.
Journal ArticleDOI
Ganoderic Acid A To Alleviate Neuroinflammation of Alzheimer's Disease in Mice by Regulating the Imbalance of the Th17/Tregs Axis.
TL;DR: In this article, the alleviating neuroinflammatory effect of Ganoderic acid A (GAA) on d-galactose mice was studied from the aspect of regulating the imbalance of the Th17/Tregs axis.
References
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