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

• Published in: Journal of neuropathology and experimental neurology Vol. 78; no. 10; pp. 910 - 921
• Main Authors: Mori, Fumiaki, Miki, Yasuo, Kon, Tomoya, Tanji, Kunikazu, Wakabayashi, Koichi
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-10-2019; by American Association of Neuropathologists, Inc
• Subjects: Amyotrophic lateral sclerosis; Autophagy; Autophagy (Cytology); Development and progression; DNA binding proteins; Genetic aspects; Health aspects; Japan; Round inclusion; Amyotrophic lateral sclerosis; Skein-like inclusion; Autophagy; TDP-43; Bunina body
• ISSN: 0022-3069; 1554-6578
• 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.