title: Neuronal and glial accumulation of alpha- and beta-synucleins in human lipidoses.
abstract: A number of the lysosomal storage diseases that have now been characterized are associated with intra-lysosomal accumulation of lipids, caused by defective lysosomal enzymes. We have previously reported neuronal accumulation of both alpha- and beta-synucleins in brain tissue of a GM2 gangliosidosis mouse model. Although alpha-synuclein has been implicated in several neurodegenerative disorders including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy, its functions remain largely unclear. In our present study, we have examined a cohort of human lipidosis cases, including Sandhoff disease, Tay-Sachs disease, metachromatic leukodystrophy, beta-galactosialidosis and adrenoleukodystrophy, for the expression of alpha- and beta-synucleins and the associated lipid storage levels. The accumulation of alpha-synuclein was found in brain tissue in not only cases of lysosomal storage diseases, but also in instances of adrenoleukodystrophy, which is a peroxisomal disease. alpha-synuclein was detected in both neurons and glial cells of patients with these two disorders, although its distribution was found to be disease-dependent. In addition, alpha-synuclein-positive neurons were also found to be NeuN-positive, whereas NeuN-negative neurons did not show any accumulation of this protein. By comparison, the accumulation of beta-synuclein was detectable only in the pons of Sandhoff disease cases. This differential accumulation of alpha- and beta-synucleins in human lipidoses may be related to functional differences between these two proteins. In addition, the accumulation of alpha-synuclein may also be a condition that is common to lysosomal storage diseases and adrenoleukodystrophies that show an enhanced expression of this protein upon the elevation of stored lipids.
authors.affiliation: Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, 236-0004, Japan. ksuzuki@med.yokohama-cu.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Suzuki
authors.forename: Eizo
authors.initials: E
authors.lastname: Iseki
authors.forename: Takashi
authors.initials: T
authors.lastname: Togo
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Omi
authors.initials: O
authors.lastname: Katsuse
authors.forename: Kayoko
authors.initials: K
authors.lastname: Katsuyama
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kanzaki
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Shiozaki
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kawanishi
authors.forename: Sumimasa
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamanaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirayasu
mesh_terms: D000328:Adult; D034961:Antigens, Nuclear / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020739:Brain Diseases, Metabolic, Inborn / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008064:Lipidoses / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020140:Lysosomal Storage Diseases, Nervous System / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D018901:Peroxisomal Disorders / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012497:Sandhoff Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051843:Synucleins / Q000032:analysis / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism; D051846:beta-Synuclein / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D009419:Nerve Tissue Proteins; D051843:Synucleins; D051844:alpha-Synuclein; D051846:beta-Synuclein; C506808:neuronal nuclear antigen NeuN, human