{"title":"伴侣蛋白TCP-1环复合物在蛋白质聚集和神经变性中的作用。","authors":"Vanlalrinchhani Varte, Diego E Rincon-Limas","doi":"10.3389/fnmol.2025.1617771","DOIUrl":null,"url":null,"abstract":"<p><p>The chaperonin TCP-1 ring complex (TRiC), also known as chaperonin-containing TCP-1 (CCT) complex, plays a crucial role in protein folding and quality control within the cell. Comprising eight distinct subunits (CCT1 - CCT8), TRiC assists in the folding of a wide range of client proteins, ensuring their proper conformation and functionality. This mini review explores the assembly, structure, and cellular functions of TRiC and discusses its involvement in protein aggregation and neurodegenerative diseases. We emphasize the emerging role of CCT2 in modulating the formation of abnormal amyloid aggregates, including amyloid beta, tau, and polyglutamine (polyQ) deposits, which are central to the pathogenesis of various neurological conditions. Lastly, we provide evidence supporting the neuroprotective role of CCT2 <i>in vivo</i> and also highlight therapeutic implications and key unresolved questions in the field, offering a foundation for new research opportunities.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1617771"},"PeriodicalIF":3.8000,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277325/pdf/","citationCount":"0","resultStr":"{\"title\":\"Role of the chaperonin TCP-1 ring complex in protein aggregation and neurodegeneration.\",\"authors\":\"Vanlalrinchhani Varte, Diego E Rincon-Limas\",\"doi\":\"10.3389/fnmol.2025.1617771\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The chaperonin TCP-1 ring complex (TRiC), also known as chaperonin-containing TCP-1 (CCT) complex, plays a crucial role in protein folding and quality control within the cell. Comprising eight distinct subunits (CCT1 - CCT8), TRiC assists in the folding of a wide range of client proteins, ensuring their proper conformation and functionality. This mini review explores the assembly, structure, and cellular functions of TRiC and discusses its involvement in protein aggregation and neurodegenerative diseases. We emphasize the emerging role of CCT2 in modulating the formation of abnormal amyloid aggregates, including amyloid beta, tau, and polyglutamine (polyQ) deposits, which are central to the pathogenesis of various neurological conditions. Lastly, we provide evidence supporting the neuroprotective role of CCT2 <i>in vivo</i> and also highlight therapeutic implications and key unresolved questions in the field, offering a foundation for new research opportunities.</p>\",\"PeriodicalId\":12630,\"journal\":{\"name\":\"Frontiers in Molecular Neuroscience\",\"volume\":\"18 \",\"pages\":\"1617771\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-07-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277325/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnmol.2025.1617771\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnmol.2025.1617771","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Role of the chaperonin TCP-1 ring complex in protein aggregation and neurodegeneration.
The chaperonin TCP-1 ring complex (TRiC), also known as chaperonin-containing TCP-1 (CCT) complex, plays a crucial role in protein folding and quality control within the cell. Comprising eight distinct subunits (CCT1 - CCT8), TRiC assists in the folding of a wide range of client proteins, ensuring their proper conformation and functionality. This mini review explores the assembly, structure, and cellular functions of TRiC and discusses its involvement in protein aggregation and neurodegenerative diseases. We emphasize the emerging role of CCT2 in modulating the formation of abnormal amyloid aggregates, including amyloid beta, tau, and polyglutamine (polyQ) deposits, which are central to the pathogenesis of various neurological conditions. Lastly, we provide evidence supporting the neuroprotective role of CCT2 in vivo and also highlight therapeutic implications and key unresolved questions in the field, offering a foundation for new research opportunities.
期刊介绍：
Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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