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自噬是肌萎缩侧索硬化症中 Bunina 小体和 TDP-43 包含物的常见降解途径。

Autophagy Is a Common Degradation Pathway for Bunina Bodies and TDP-43 Inclusions in Amyotrophic Lateral Sclerosis.

机构信息

Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.

出版信息

J Neuropathol Exp Neurol. 2019 Oct 1;78(10):910-921. doi: 10.1093/jnen/nlz072.

Abstract

Bunina bodies (BBs) coexisting with TDP-43-immunoreactive (TDP-43-IR) skein-like inclusions (SIs) and round inclusions (RIs) in lower motor neurons are a frequent feature of sporadic amyotrophic lateral sclerosis (sALS). Since previous studies have shown that BBs and TDP-43-IR inclusions are often detected in association with autophagy-related structures (autophagosomes and autolysosomes), we examined the anterior horn cells (AHCs) of the spinal cord from 15 patients with sALS and 6 control subjects, using antibodies against autophagy-related proteins (LC3, cathepsin B, and cathepsin D). Among AHCs with SIs, 43.9% contained BBs, whereas 51.7% of AHCs with RIs did so. The cytoplasm of AHCs showed diffuse immunoreactivity for LC3, cathepsin B and cathepsin D in both sALS and controls. Ultrastructurally, SIs and mature BBs contained autophagosomes and autolysosomes. Mature BBs were localized in the vicinity of SIs. RIs also contained autophagosomes, autolysosomes, and early-stage BBs. These findings suggest that autophagy is a common degradation pathway for BBs and TDP-43-IR inclusions, which may explain their frequent coexistence.

摘要

Bunina 小体(BBs)与 TDP-43 免疫反应性(TDP-43-IR)缠结样包含体(SIs)和圆形包含体(RIs)共存于下运动神经元中,是散发性肌萎缩侧索硬化症(sALS)的常见特征。由于先前的研究表明 BBs 和 TDP-43-IR 包含体通常与自噬相关结构(自噬体和自溶酶体)一起检测到,因此我们使用针对自噬相关蛋白(LC3、组织蛋白酶 B 和组织蛋白酶 D)的抗体检查了来自 15 名 sALS 患者和 6 名对照者的脊髓前角细胞(AHCs)。在具有 SIs 的 AHCs 中,有 43.9%包含 BBs,而在具有 RIs 的 AHCs 中,有 51.7%包含 BBs。LC3、组织蛋白酶 B 和组织蛋白酶 D 在 sALS 和对照组中均在 AHCs 的细胞质中表现出弥漫性免疫反应性。超微结构显示,SIs 和成熟的 BBs 均包含自噬体和自溶酶体。成熟的 BBs 定位于 SIs 的附近。RIs 还包含自噬体、自溶酶体和早期 BBs。这些发现表明自噬是 BBs 和 TDP-43-IR 包含体的常见降解途径,这可能解释了它们的频繁共存。

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