Neuronal cell death mechanisms in Alzheimer’s disease: An insight
Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.937133/full |
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| author | Parul Goel Sasanka Chakrabarti Kapil Goel Karanpreet Bhutani Tanya Chopra Sharadendu Bali |
| author_facet | Parul Goel Sasanka Chakrabarti Kapil Goel Karanpreet Bhutani Tanya Chopra Sharadendu Bali |
| author_sort | Parul Goel |
| collection | DOAJ |
| description | Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer’s disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid β peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-β plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer’s Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD. |
| first_indexed | 2024-04-13T02:39:18Z |
| format | Article |
| id | doaj.art-3decbd3fde1b428ca1afb00e05020587 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-04-13T02:39:18Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-3decbd3fde1b428ca1afb00e050205872022-12-22T03:06:15ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-08-011510.3389/fnmol.2022.937133937133Neuronal cell death mechanisms in Alzheimer’s disease: An insightParul Goel0Sasanka Chakrabarti1Kapil Goel2Karanpreet Bhutani3Tanya Chopra4Sharadendu Bali5Department of Biochemistry, Shri Atal Bihari Vajpayee Government Medical College Chhainsa, Faridabad, IndiaDepartment of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Ambala, IndiaDepartment of Community Medicine and School of Public Health, Post Graduate Institute of Medical Education and Research, Chandigarh, IndiaDepartment of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Ambala, IndiaDepartment of Biochemistry, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Ambala, IndiaDepartment of Surgery, Maharishi Markandeshwar Institute of Medical Sciences and Research, Maharishi Markandeshwar (Deemed to be University), Ambala, IndiaRegulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer’s disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid β peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-β plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer’s Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD.https://www.frontiersin.org/articles/10.3389/fnmol.2022.937133/fullAlzheimer’s diseaseapoptosisnecroptosisautophagyferroptosis |
| spellingShingle | Parul Goel Sasanka Chakrabarti Kapil Goel Karanpreet Bhutani Tanya Chopra Sharadendu Bali Neuronal cell death mechanisms in Alzheimer’s disease: An insight Frontiers in Molecular Neuroscience Alzheimer’s disease apoptosis necroptosis autophagy ferroptosis |
| title | Neuronal cell death mechanisms in Alzheimer’s disease: An insight |
| title_full | Neuronal cell death mechanisms in Alzheimer’s disease: An insight |
| title_fullStr | Neuronal cell death mechanisms in Alzheimer’s disease: An insight |
| title_full_unstemmed | Neuronal cell death mechanisms in Alzheimer’s disease: An insight |
| title_short | Neuronal cell death mechanisms in Alzheimer’s disease: An insight |
| title_sort | neuronal cell death mechanisms in alzheimer s disease an insight |
| topic | Alzheimer’s disease apoptosis necroptosis autophagy ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.937133/full |
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