ALS-associated protein FIG4 is localized in Pick and Lewy bodies, and also neuronal nuclear inclusions, in polyglutamine and intranuclear inclusion body diseases

• Published in: Neuropathology Vol. 34; no. 1; pp. 19 - 26
• Main Authors: Kon, Tomoya, Mori, Fumiaki, Tanji, Kunikazu, Miki, Yasuo, Toyoshima, Yasuko, Yoshida, Mari, Sasaki, Hidenao, Kakita, Akiyoshi, Takahashi, Hitoshi, Wakabayashi, Koichi
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.02.2014; Wiley Subscription Services, Inc
• Subjects: Aged; Aged, 80 and over; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - enzymology; Amyotrophic Lateral Sclerosis - pathology; Brain - enzymology; Brain - pathology; Disease; endosomal-lysosomal pathway; FIG4; Flavoproteins - analysis; Humans; Intranuclear Inclusion Bodies - enzymology; Intranuclear Inclusion Bodies - pathology; Lewy Bodies - enzymology; Lewy Bodies - pathology; Lewy body; Medical research; Middle Aged; Neurodegenerative Diseases - enzymology; Neurodegenerative Diseases - pathology; Neurons - enzymology; Neurons - pathology; nuclear inclusion; Peptides - metabolism; Phosphoric Monoester Hydrolases - analysis; Pick body; Pick Disease of the Brain - enzymology; Pick Disease of the Brain - pathology; Proteins; FIG4; endosomal-lysosomal pathway; nuclear inclusion; Lewy body; Pick body
• ISSN: 0919-6544; 1440-1789; 1440-1789
• DOI: 10.1111/neup.12056

FIG4 is a phosphatase that regulates intracellular vesicle trafficking along the endosomal‐lysosomal pathway. Mutations of FIG4 lead to the development of Charcot‐Marie‐Tooth disease type 4J and amyotrophic lateral sclerosis (ALS). Moreover, ALS‐associated proteins (transactivation response DNA protein 43 (TDP‐43), fused in sarcoma (FUS), optineurin, ubiquilin‐2, charged mutivesicular body protein 2b (CHMP2B) and valosin‐containing protein) are involved in inclusion body formation in several neurodegenerative diseases. Using immunohistochemistry, we examined the brains and spinal cords of patients with various neurodegenerative diseases, including sporadic TDP‐43 proteinopathy (ALS and frontotemporal lobar degeneration). TDP‐43 proteinopathy demonstrated no FIG4 immunoreactivity in neuronal inclusions. However, FIG4 immunoreactivity was present in Pick bodies in Pick's disease, Lewy bodies in Parkinson's disease and dementia with Lewy bodies, neuronal nuclear inclusions in polyglutamine and intranuclear inclusion body diseases, and Marinesco and Hirano bodies in aged control subjects. These findings suggest that FIG4 is not incorporated in TDP‐43 inclusions and that it may have a common role in the formation or degradation of neuronal cytoplasmic and nuclear inclusions in several neurodegenerative diseases.