An N-terminal fragment of ProSAAS (a granin-like neuroendocrine peptide precursor) is associated with tau inclusions in Pick's disease |
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Authors: | Kikuchi Kenji Arawaka Shigeki Koyama Shingo Kimura Hideki Ren Chang-Hong Wada Manabu Kawanami Toru Kurita Keiji Daimon Makoto Kawakatsu Shinobu Kadoya Toshihiko Goto Kaoru Kato Takeo |
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Institution: | Third Department of Internal Medicine, Yamagata University School of Medicine, Japan. |
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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. |
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Keywords: | ProSAAS Tau Tauopathy Pick body Pick’s disease Neurodegeneration |
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