Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review
Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Ta...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2024-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1221;epage=1232;aulast=Chu |
| _version_ | 1797231744006488064 |
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| author | Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu |
| author_facet | Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu |
| author_sort | Dandan Chu |
| collection | DOAJ |
| description | Alzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease. |
| first_indexed | 2024-04-24T15:49:14Z |
| format | Article |
| id | doaj.art-6fef2a4444084826a17ec59fd7d262a7 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-04-24T15:49:14Z |
| publishDate | 2024-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-6fef2a4444084826a17ec59fd7d262a72024-04-01T13:05:59ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742024-01-011961221123210.4103/1673-5374.385853Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative reviewDandan ChuXingyue YangJing WangYan ZhouJin-Hua GuJin MiaoFeng WuFei LiuAlzheimer’s disease is characterized by two major neuropathological hallmarks—the extracellular β-amyloid plaques and intracellular neurofibrillary tangles consisting of aggregated and hyperphosphorylated Tau protein. Recent studies suggest that dysregulation of the microtubule-associated protein Tau, especially specific proteolysis, could be a driving force for Alzheimer’s disease neurodegeneration. Tau physiologically promotes the assembly and stabilization of microtubules, whereas specific truncated fragments are sufficient to induce abnormal hyperphosphorylation and aggregate into toxic oligomers, resulting in them gaining prion-like characteristics. In addition, Tau truncations cause extensive impairments to neural and glial cell functions and animal cognition and behavior in a fragment-dependent manner. This review summarizes over 60 proteolytic cleavage sites and their corresponding truncated fragments, investigates the role of specific truncations in physiological and pathological states of Alzheimer’s disease, and summarizes the latest applications of strategies targeting Tau fragments in the diagnosis and treatment of Alzheimer’s disease.http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1221;epage=1232;aulast=Chualzheimer’s disease; cleavage site; diagnosis; marker; neurofibrillary tangles; phosphorylation; tau; tau aggregation; therapy; truncation |
| spellingShingle | Dandan Chu Xingyue Yang Jing Wang Yan Zhou Jin-Hua Gu Jin Miao Feng Wu Fei Liu Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review Neural Regeneration Research alzheimer’s disease; cleavage site; diagnosis; marker; neurofibrillary tangles; phosphorylation; tau; tau aggregation; therapy; truncation |
| title | Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review |
| title_full | Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review |
| title_fullStr | Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review |
| title_full_unstemmed | Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review |
| title_short | Tau truncation in the pathogenesis of Alzheimer’s disease: a narrative review |
| title_sort | tau truncation in the pathogenesis of alzheimer s disease a narrative review |
| topic | alzheimer’s disease; cleavage site; diagnosis; marker; neurofibrillary tangles; phosphorylation; tau; tau aggregation; therapy; truncation |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=6;spage=1221;epage=1232;aulast=Chu |
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