title: ALS-associated protein FIG4 is localized in Pick and Lewy bodies, and also neuronal nuclear inclusions, in polyglutamine and intranuclear inclusion body diseases.
abstract: 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.
authors.affiliation: Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Kon
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miki
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Toyoshima
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hidenao
authors.initials: H
authors.lastname: Sasaki
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005420:Flavoproteins / Q000032:analysis*; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000201:enzymology* / Q000473:pathology; D016631:Lewy Bodies / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000201:enzymology* / Q000473:pathology*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000032:analysis*; D020774:Pick Disease of the Brain / Q000201:enzymology / Q000473:pathology
chemical_list: D005420:Flavoproteins; D010455:Peptides; C097188:polyglutamine; C522215:FIG4 protein, human; D010744:Phosphoric Monoester Hydrolases
keywords: FIG4; Lewy body; Pick body; endosomal-lysosomal pathway; nuclear inclusion