TDP-43 is an RNA-binding protein that forms toxic aggregates in the neuronal cytoplasm that are commonly detected in multiple neurodegenerative diseases. Mislocalization of TDP-43 to the cytoplasm is thought to disrupt RNA processing, which may also contribute to its pathological effects. Loss of nuclear TDP-43 causes alternative splicing of the gene STMN2, which encodes stathmin-2, a key protein that regulates axon growth and regeneration; this splicing leads to a nonfunctional truncated variant. However, it was unclear how TDP-43 directly alters STMN2 splicing.

中文翻译：

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隐蔽目标

TDP-43 是一种 RNA 结合蛋白，可在神经细胞质中形成毒性聚集体，通常在多种神经退行性疾病中检测到。TDP-43 错误定位到细胞质被认为会破坏 RNA 加工，这也可能导致其病理效应。核 TDP-43 的缺失导致基因STMN2的可变剪接，该基因编码 stathmin-2，一种调节轴突生长和再生的关键蛋白；这种剪接导致了一个无功能的截断变体。然而，尚不清楚 TDP-43 如何直接改变STMN2剪接。