{"title":"阿尔茨海默病中三羧酸循环(TCA)循环的损伤:机制、意义和潜在的治疗方法。","authors":"Gudimetla Susmitha Mohan, Rahul Kumar","doi":"10.14336/AD.2025.0472","DOIUrl":null,"url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition defined by the gradual impairment of cognitive functions, synaptic disarray, and extensive neuronal loss. Emerging evidence suggests that metabolic impairment, specifically within tricarboxylic acid (TCA) cycle, is instrumental in the AD pathophysiology. TCA cycle represents an indispensable pathway in metabolism that is responsible for energy production, and the maintenance of cellular homeostasis, particularly in neurons. Several in vitro, clinical, and in vivo studies reported that several TCA cycle enzymes disrupt during AD. Disruption in TCA cycle enzymes exhibits more pronounced impact on the brain owing to its high metabolic activity and continuous demand for energy, where any reduction in ATP production can severely impair neuronal function, synaptic plasticity, and overall cognitive processes. The current review explores the mechanisms underlying AD related impairment in TCA cycle, focussing on the molecular alterations of TCA enzymes. We also discussed potential activators and inhibitors of TCA cycle enzymes as a potential therapeutic intervention to restore AD related metabolic balance.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.\",\"authors\":\"Gudimetla Susmitha Mohan, Rahul Kumar\",\"doi\":\"10.14336/AD.2025.0472\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Alzheimer's disease (AD) is a neurodegenerative condition defined by the gradual impairment of cognitive functions, synaptic disarray, and extensive neuronal loss. Emerging evidence suggests that metabolic impairment, specifically within tricarboxylic acid (TCA) cycle, is instrumental in the AD pathophysiology. TCA cycle represents an indispensable pathway in metabolism that is responsible for energy production, and the maintenance of cellular homeostasis, particularly in neurons. Several in vitro, clinical, and in vivo studies reported that several TCA cycle enzymes disrupt during AD. Disruption in TCA cycle enzymes exhibits more pronounced impact on the brain owing to its high metabolic activity and continuous demand for energy, where any reduction in ATP production can severely impair neuronal function, synaptic plasticity, and overall cognitive processes. The current review explores the mechanisms underlying AD related impairment in TCA cycle, focussing on the molecular alterations of TCA enzymes. We also discussed potential activators and inhibitors of TCA cycle enzymes as a potential therapeutic intervention to restore AD related metabolic balance.</p>\",\"PeriodicalId\":7434,\"journal\":{\"name\":\"Aging and Disease\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":6.9000,\"publicationDate\":\"2025-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Aging and Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.14336/AD.2025.0472\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GERIATRICS & GERONTOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Aging and Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.14336/AD.2025.0472","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
Impairment of Tricarboxylic Acid Cycle (TCA) Cycle in Alzheimer's Disease: Mechanisms, Implications, and Potential Therapies.
Alzheimer's disease (AD) is a neurodegenerative condition defined by the gradual impairment of cognitive functions, synaptic disarray, and extensive neuronal loss. Emerging evidence suggests that metabolic impairment, specifically within tricarboxylic acid (TCA) cycle, is instrumental in the AD pathophysiology. TCA cycle represents an indispensable pathway in metabolism that is responsible for energy production, and the maintenance of cellular homeostasis, particularly in neurons. Several in vitro, clinical, and in vivo studies reported that several TCA cycle enzymes disrupt during AD. Disruption in TCA cycle enzymes exhibits more pronounced impact on the brain owing to its high metabolic activity and continuous demand for energy, where any reduction in ATP production can severely impair neuronal function, synaptic plasticity, and overall cognitive processes. The current review explores the mechanisms underlying AD related impairment in TCA cycle, focussing on the molecular alterations of TCA enzymes. We also discussed potential activators and inhibitors of TCA cycle enzymes as a potential therapeutic intervention to restore AD related metabolic balance.
期刊介绍:
Aging & Disease (A&D) is an open-access online journal dedicated to publishing groundbreaking research on the biology of aging, the pathophysiology of age-related diseases, and innovative therapies for conditions affecting the elderly. The scope encompasses various diseases such as Stroke, Alzheimer's disease, Parkinson’s disease, Epilepsy, Dementia, Depression, Cardiovascular Disease, Cancer, Arthritis, Cataract, Osteoporosis, Diabetes, and Hypertension. The journal welcomes studies involving animal models as well as human tissues or cells.