数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
证据级别：摘要级。本条依据 PubMed 结构化摘要与元数据撰写，付费墙全文未获取、未逐节核验，本站未做任何数值推算补全。
研究问题
TAR DNA-binding protein 43 (TDP-43) pathology is a defining feature of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
方法
Although TDP-43 dysfunction has traditionally been studied through a neuron-centric framework, increasing evidence demonstrates that astrocytes, microglia, and oligodendrocytes are also directly affected and actively contribute to disease progression.
核心结论
In this review, we examine how TDP-43 dysfunction disrupts lineage-specific glial homeostatic programs and promotes distinct pathological state transitions across major glial populations.；In astrocytes, TDP-43 dysfunction impairs neurotransmitter regulation, metabolic and neuronal support, RNA homeostasis, and secretory signaling while promoting inflammatory and antiviral-like states.；In microglia, altered TDP-43 disrupts inflammatory regulation, phagocytosis, lysosomal function, lipid metabolism, and stage-dependent protective responses.；In oligodendrocytes, TDP-43 dysfunction compromises RNA processing, lineage maintenance, lipid metabolism, myelin integrity, and long-term axonal support. ‖ 结论：Together, these findings suggest that glial TDP-43 dysfunction cannot be reduced to a single generalized form of reactivity but instead reflects the breakdown of distinct cell type-specific identities required to maintain central nervous system homeostasis.
局限
未能获取全文，具体设计细节、失访与统计学处理无法核验。
对本项目的价值
★★★☆☆ 脑老化是最大未满足需求，也是终点最难量化的领域；biomarker 与认知读数选择最敏感。
原文题录
- 英文标题：TDP-43 dysfunction destabilizes glial homeostatic identity in ALS/FTD.
- 期刊与标识：Brain Res · PMID 42946239 · DOI 10.1016/j.brainres.2026.150618**
C 级证据分级：C 级（预印本 / 观点评论，非原始研究）
本文属观点/评论类文献，不是原始研究。其论点依赖于作者对既有证据的梳理与判断，不构成新的实验证据。本站标注 C 级即为此意——阅读时请把它当作「领域内的思考框架」，而非「研究发现」。
关于本文的文献来源：本站依据 IMA 知识库「五刊监控·深度文献卡片」（SOP §4.2 摘要级）撰写，依据期刊公开摘要与 PubMed 元数据；付费墙全文未获取之处已标注「待补全文」，未做任何数值推算补全。