title: An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease.
abstract: The deposition of aggregated tau in cytoplasmic inclusions is one of the common neuropathological features in various dementing neurodegenerative disorders. At present, it remains unclear whether tau inclusions exert neurotoxicity or they are simply the consequence of neurodegeneration. In our approach for the analysis of the composition of tau inclusions, we detected the intense binding of anti-diacylglycerol kinase-zeta (DGK-zeta) antibodies to Pick bodies (PBs), which represent tau inclusions in Pick's disease. The polyclonal antibodies were found to cross-react with a 21-kDa protein, but not with tau or ubiquitin, on Western blots of normal human brain extracts. Analysis of the 21-kDa protein by two-dimensional-gel electrophoresis and mass-spectrometry revealed that the protein is an N-terminal fragment of proSAAS (a human granin-like neuroendocrine peptide precursor). Our results suggest that sequestration of the N-terminal fragment of proSAAS in intracellular PBs may cause a functional disturbance of neurons in Pick's disease.
authors.affiliation: Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Arawaka
authors.forename: Shingo
authors.initials: S
authors.lastname: Koyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.forename: Chang-Hong
authors.initials: CH
authors.lastname: Ren
authors.forename: Manabu
authors.initials: M
authors.lastname: Wada
authors.forename: Toru
authors.initials: T
authors.lastname: Kawanami
authors.forename: Keiji
authors.initials: K
authors.lastname: Kurita
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kawakatsu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kadoya
authors.forename: Kaoru
authors.initials: K
authors.lastname: Goto
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D019852:Diacylglycerol Kinase / Q000276:immunology; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry* / Q000473:pathology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology; D020774:Pick Disease of the Brain / Q000473:pathology*; D011498:Protein Precursors / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D014452:Ubiquitins / Q000276:immunology; D016875:tau Proteins / Q000032:analysis / Q000276:immunology
chemical_list: D000906:Antibodies; D009479:Neuropeptides; C403532:PCSK1N protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; D014452:Ubiquitins; D016875:tau Proteins; D019852:Diacylglycerol Kinase