Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies
Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Neural Circuits |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncir.2023.1099467/full |
| _version_ | 1797934938621739008 |
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| author | Swagata Ghatak Tomohiro Nakamura Stuart A. Lipton Stuart A. Lipton |
| author_facet | Swagata Ghatak Tomohiro Nakamura Stuart A. Lipton Stuart A. Lipton |
| author_sort | Swagata Ghatak |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD. |
| first_indexed | 2024-04-10T18:06:42Z |
| format | Article |
| id | doaj.art-07473a5bd1a647c39314162731d0d6d0 |
| institution | Directory Open Access Journal |
| issn | 1662-5110 |
| language | English |
| last_indexed | 2024-04-10T18:06:42Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neural Circuits |
| spelling | doaj.art-07473a5bd1a647c39314162731d0d6d02023-02-02T12:28:17ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102023-02-011710.3389/fncir.2023.10994671099467Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapiesSwagata Ghatak0Tomohiro Nakamura1Stuart A. Lipton2Stuart A. Lipton3School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, IndiaNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United StatesNeurodegeneration New Medicines Center and Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United StatesDepartment of Neurosciences, School of Medicine, University of California, San Diego, La Jolla, CA, United StatesAlzheimer’s disease (AD) is arguably the most common cause of dementia in the elderly and is marked by progressive synaptic degeneration, which in turn leads to cognitive decline. Studies in patients and in various AD models have shown that one of the early signatures of AD is neuronal hyperactivity. This excessive electrical activity contributes to dysregulated neural network function and synaptic damage. Mechanistically, evidence suggests that hyperexcitability accelerates production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute to neural network impairment and synapse loss. This review focuses on the pathways and molecular changes that cause hyperexcitability and how RNS-dependent posttranslational modifications, represented predominantly by protein S-nitrosylation, mediate, at least in part, the deleterious effects of hyperexcitability on single neurons and the neural network, resulting in synaptic loss in AD.https://www.frontiersin.org/articles/10.3389/fncir.2023.1099467/fullhyperexcitabilityAlzheimer’s diseaseS-nitrosylationNMDA receptorsglutamate excitotoxicityNitroSynapsin |
| spellingShingle | Swagata Ghatak Tomohiro Nakamura Stuart A. Lipton Stuart A. Lipton Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies Frontiers in Neural Circuits hyperexcitability Alzheimer’s disease S-nitrosylation NMDA receptors glutamate excitotoxicity NitroSynapsin |
| title | Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies |
| title_full | Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies |
| title_fullStr | Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies |
| title_full_unstemmed | Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies |
| title_short | Aberrant protein S-nitrosylation contributes to hyperexcitability-induced synaptic damage in Alzheimer’s disease: Mechanistic insights and potential therapies |
| title_sort | aberrant protein s nitrosylation contributes to hyperexcitability induced synaptic damage in alzheimer s disease mechanistic insights and potential therapies |
| topic | hyperexcitability Alzheimer’s disease S-nitrosylation NMDA receptors glutamate excitotoxicity NitroSynapsin |
| url | https://www.frontiersin.org/articles/10.3389/fncir.2023.1099467/full |
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