Aberrant accumulation of ErbB4 in progressive supranuclear palsy

A. Murakami, M. Nakamura, S. Kaneko, W. L. Lin, Dennis W Dickson, H. Kusaka

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalNeuropathology and Applied Neurobiology
DOIs
StateAccepted/In press - Jan 1 2018

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Progressive Supranuclear Palsy
Neuregulin-1
Cytoplasm
Proteins
Coiled Bodies
Neurons
Neurofibrillary Tangles
Amyotrophic Lateral Sclerosis
Brain
Epidermal Growth Factor Receptor
Neuroglia
Neurodegenerative Diseases
Fluorescent Antibody Technique
Parkinson Disease
Alzheimer Disease

Keywords

  • ErbB4
  • ErbB4 intracellular C-terminal domain
  • Globose neurofibrillary tangles
  • Neuregulin-1
  • Progressive supranuclear palsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Aberrant accumulation of ErbB4 in progressive supranuclear palsy. / Murakami, A.; Nakamura, M.; Kaneko, S.; Lin, W. L.; Dickson, Dennis W; Kusaka, H.

In: Neuropathology and Applied Neurobiology, 01.01.2018.

Research output: Contribution to journalArticle

Murakami, A. ; Nakamura, M. ; Kaneko, S. ; Lin, W. L. ; Dickson, Dennis W ; Kusaka, H. / Aberrant accumulation of ErbB4 in progressive supranuclear palsy. In: Neuropathology and Applied Neurobiology. 2018.
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