{"title":"Tau蛋白聚集:神经退行性疾病的治疗靶点。","authors":"Aryan Duggal, Drishti Mahindru, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.11.012","DOIUrl":null,"url":null,"abstract":"<p><p>Tau protein, a critical element for neuronal structure, becomes pathogenic in numerous neurodegenerative diseases, particularly Alzheimer's disease and other tauopathies. Under normal conditions, tau stabilizes microtubules and supports essential cellular transport systems. However, in disease states, tau undergoes abnormal modifications-most notably hyperphosphorylation-causing it to detach from microtubules and aggregate into neurofibrillary tangles. These aggregates disrupt neuronal function, leading to progressive cognitive and motor deficits. This chapter provides a comprehensive overview of tau's structural properties, normal cellular roles, and the cascade of pathological changes that transform it into a neurotoxic agent. We examine current therapeutic strategies targeting tau, including efforts to inhibit its phosphorylation, prevent aggregation, and enhance its clearance from cells. Approaches such as kinase inhibitors, immunotherapies, and gene-based therapies are discussed in the context of their potential to halt or slow disease progression. Additionally, recent advancements in diagnostic tools-such as tau-specific PET imaging and blood biomarkers-are highlighted as transformative for early detection of the disease .</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"146 ","pages":"77-136"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Tau protein aggregation: A therapeutic target for neurodegenerative diseases.\",\"authors\":\"Aryan Duggal, Drishti Mahindru, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati\",\"doi\":\"10.1016/bs.apcsb.2024.11.012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tau protein, a critical element for neuronal structure, becomes pathogenic in numerous neurodegenerative diseases, particularly Alzheimer's disease and other tauopathies. Under normal conditions, tau stabilizes microtubules and supports essential cellular transport systems. However, in disease states, tau undergoes abnormal modifications-most notably hyperphosphorylation-causing it to detach from microtubules and aggregate into neurofibrillary tangles. These aggregates disrupt neuronal function, leading to progressive cognitive and motor deficits. This chapter provides a comprehensive overview of tau's structural properties, normal cellular roles, and the cascade of pathological changes that transform it into a neurotoxic agent. We examine current therapeutic strategies targeting tau, including efforts to inhibit its phosphorylation, prevent aggregation, and enhance its clearance from cells. Approaches such as kinase inhibitors, immunotherapies, and gene-based therapies are discussed in the context of their potential to halt or slow disease progression. Additionally, recent advancements in diagnostic tools-such as tau-specific PET imaging and blood biomarkers-are highlighted as transformative for early detection of the disease .</p>\",\"PeriodicalId\":7376,\"journal\":{\"name\":\"Advances in protein chemistry and structural biology\",\"volume\":\"146 \",\"pages\":\"77-136\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in protein chemistry and structural biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/bs.apcsb.2024.11.012\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in protein chemistry and structural biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.apcsb.2024.11.012","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Tau protein aggregation: A therapeutic target for neurodegenerative diseases.
Tau protein, a critical element for neuronal structure, becomes pathogenic in numerous neurodegenerative diseases, particularly Alzheimer's disease and other tauopathies. Under normal conditions, tau stabilizes microtubules and supports essential cellular transport systems. However, in disease states, tau undergoes abnormal modifications-most notably hyperphosphorylation-causing it to detach from microtubules and aggregate into neurofibrillary tangles. These aggregates disrupt neuronal function, leading to progressive cognitive and motor deficits. This chapter provides a comprehensive overview of tau's structural properties, normal cellular roles, and the cascade of pathological changes that transform it into a neurotoxic agent. We examine current therapeutic strategies targeting tau, including efforts to inhibit its phosphorylation, prevent aggregation, and enhance its clearance from cells. Approaches such as kinase inhibitors, immunotherapies, and gene-based therapies are discussed in the context of their potential to halt or slow disease progression. Additionally, recent advancements in diagnostic tools-such as tau-specific PET imaging and blood biomarkers-are highlighted as transformative for early detection of the disease .
期刊介绍:
Published continuously since 1944, The Advances in Protein Chemistry and Structural Biology series has been the essential resource for protein chemists. Each volume brings forth new information about protocols and analysis of proteins. Each thematically organized volume is guest edited by leading experts in a broad range of protein-related topics.