An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease.
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.
Kikuchi
Kenji
K
Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
Arawaka
Shigeki
S
Koyama
Shingo
S
Kimura
Hideki
H
Ren
Chang-Hong
CH
Wada
Manabu
M
Kawanami
Toru
T
Kurita
Keiji
K
Daimon
Makoto
M
Kawakatsu
Shinobu
S
Kadoya
Toshihiko
T
Goto
Kaoru
K
Kato
Takeo
T
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
D000906:Antibodies; D009479:Neuropeptides; C403532:PCSK1N protein, human; D010446:Peptide Fragments; D011498:Protein Precursors; D014452:Ubiquitins; D016875:tau Proteins; D019852:Diacylglycerol Kinase