The relationship between RNA-binding proteins, particularly TAR DNA binding protein 43 (TDP-43), and neurodegeneration is an important area of research. TDP-43 is involved in so many cellular processes that perturbation of protein homeostasis can lead to countless downstream effects. Understanding what leads to this disease-related protein imbalance and the resulting cellular and molecular effects will help to develop targets for disease intervention, whether it be prevention of protein accumulation, or addressing a secondary effect of protein accumulation. Here we review the current literature of TDP-43 and TDP-43 pathologies, the effects of TDP-43 overexpression and disruption of synaptic proteins through its binding of messenger RNA, leading to synaptic dysfunction. This review highlights some of the still-limited knowledge of the protein TDP-43 and how it can contribute to disease.

中文翻译：

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TDP-43在MND-FTLD病理学范围内。

RNA结合蛋白，特别是TAR DNA结合蛋白43（TDP-43）与神经变性之间的关系是重要的研究领域。TDP-43参与了许多细胞过程，以至于蛋白质稳态的扰动可能导致无数下游效应。了解导致这种与疾病相关的蛋白质失衡的原因以及由此产生的细胞和分子效应将有助于制定疾病干预目标，无论是预防蛋白质蓄积还是解决蛋白质蓄积的次级效应。在这里，我们回顾了TDP-43和TDP-43病理学的最新文献，TDP-43过表达和通过其信使RNA的结合导致突触功能障碍的突触蛋白破坏的影响。