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嵌合抗原受体细胞治疗:现状及其在衰老和阿尔茨海默病中的潜力

英文原题:Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease.

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Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease.

PubMed 2025/09/16(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

随着人口老龄化,神经退行性疾病患病率在全球范围内上升。阿尔茨海默病(AD)是最常见的痴呆类型。衰老研究发现,衰老细胞会随时间逐渐积累;这些细胞退出细胞周期但仍保持代谢活性,并通过衰老相关分泌表型将衰老特征传播给邻近细胞。多种组织中积累的衰老细胞参与若干年龄相关疾病的发生,因此清除这些细胞可能成为有吸引力的抗衰老策略。鉴于工程化嵌合抗原受体(CAR)T细胞治疗血液系统恶性肿瘤的成功,科学界尝试将这一策略用于对抗衰老及年龄相关疾病。该领域仍处于起步阶段,但体外和动物模型结果令人鼓舞。考虑到CAR-T 疗法可能引起严重副作用(细胞因子释放综合征、免疫细胞相关神经系统综合征),且AD治疗应避免清除带有神经原纤维缠结和淀粉样蛋白聚集体的神经元(因这些细胞再生能力有限),CAR巨噬细胞、CAR调节性T细胞或这些细胞来源的外泌体可能是更有前景的方案。

展开英文摘要原文

With an aging population, there is a worldwide increase in the prevalence of neurodegenerative diseases. Alzheimer's disease (AD) is the most prevalent form of dementia. Research focusing on aging has revealed a time-related accumulation of senescent cells that escape the cell cycle but remain metabolically active and spread the senescent traits to neighboring cells via the senescence-associated secretory phenotype. The accumulated senescent cells in various tissues are involved in the pathogenesis of several age-related conditions. As such, eliminating them would be an appealing anti-aging strategy.

Following the high success rates of engineered chimeric antigen receptor (CAR)-T cells in hematological malignancies, the scientific community has tried to adapt the strategy to fight aging and age-related diseases. Research in this area is only in its infancy, but the results obtained from in vitro and animal models are encouraging.

Due to the serious side effects of CAR-T cell therapies (cytokine release syndrome, immune cell-associated neurological syndrome) and because in AD the elimination of neurons with neurofibrillary tangles and amyloid aggregates should be avoided (given the limited regenerative potential of these cells), CAR macrophages, CAR regulatory T cells, or exosomes derived from these cells are a more promising approach.

论文信息

作者
Jurcau MC、Iovanovici CD、Jurcau A、Militaru M、Udrea RB、Comanescu A、Nunkoo VS
第一作者单位
Faculty of Medicine and Pharmacy, University of Oradea, 1 Decembrie Square nr. 10, 410073 Oradea, Romania.Italy
通讯作者单位
Doctoral School of Biomedical Sciences, University of Oradea, Universitatii Street nr. 1, 410087 Oradea, Romania.Italy
文献类型
综述
期刊
International journal of molecular sciences2025 Sep 16
原文标识
PubMed 41009574 · DOI 10.3390/ijms26189009