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Aberrant accumulation of ErbB4 in progressive supranuclear palsy
Author(s) -
Murakami A.,
Nakamura M.,
Kaneko S.,
Lin W.L.,
Dickson D. W.,
Kusaka H.
Publication year - 2018
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/nan.12460
Subject(s) - erbb4 , progressive supranuclear palsy , erbb , cytoplasm , neuregulin 1 , biology , pathology , pathogenesis , amyotrophic lateral sclerosis , cytoplasmic inclusion , neuregulin , neuroscience , microbiology and biotechnology , medicine , disease , signal transduction , receptor tyrosine kinase
Aims The human epidermal growth factor receptor family consists of four members that belong to the ErbB lineage of proteins (ErbB1‐4). Neuregulin‐1 (NRG1)/ErbB signalling regulates brain development and function. Abnormalities in this signalling have been implicated in the aetiology or development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. So, we aimed at investigating whether the expression of NRG1 or ErbB proteins are altered in progressive supranuclear palsy (PSP). Methods The brains of 10 PSP and six control patients were investigated by immunohistochemical analysis. Results Whereas C‐terminal ErbB4 immunoreacitivity was partially but distinctly present in the cytoplasm and/or in the nucleus of neurons in control patients, it was rarely observed in the neuronal nuclei in PSP patients. In contrast, neurofibrillary tangles, coiled bodies and threads were robustly immunoreactive for C‐terminal ErbB4 in PSP. Double immunofluorescence for C‐terminal ErbB4 and phospho‐tau revealed co‐localization of these proteins within neuronal and glial inclusions. To the contrary, there was no difference in the subcellular localization of NRG1, ErbB1, ErbB2, and N‐terminal ErbB4 between control and PSP patients. These proteins were localized in the cytoplasm of neurons. Conclusions Our present results suggest that NRG1/ErbB4 signalling could be an important event in the pathogenesis of PSP.