Astrocytic expression of interferon-induced myxovirus resistance protein A and protein kinase R in prion diseases: Distinct plaque-associated myxovirus resistance protein A localization in Gerstmann-Sträussler-Scheinker disease.

Authors

Naonori Sakurada, Akihiro Watanabe, Motoi Yoshimura, Nobutaka Sakae, Hajime Arahata, Akifumi Yamamoto, Takaaki Kanemaru, Hideko Noguchi, Shinichiro Mori, Masahiro Shijo, Takeshi Fujimoto, Keita Kai, Shinichi Aishima, Haruki Koike, Yoshio Tsuboi, Hiroaki Miyoshi, Naokazu Sasagasako, Hiroyuki Honda

Published in

Journal of neuropathology and experimental neurology. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Human prion diseases, including sporadic Creutzfeldt-Jakob disease (sCJD) and Gerstmann-Sträussler-Scheinker disease (GSS), are fatal neurodegenerative disorders characterized by misfolded prion protein (PrP) accumulation. Although type I interferon (IFN) signaling and downstream IFN-stimulated genes are well characterized as essential components of host defense in experimental animal models, their roles in human prion pathology remain poorly defined. Myxovirus resistance protein A (MxA) and protein kinase R (PKR) have immunomodulatory functions, yet their histopathological expression in prion diseases is insufficiently characterized. We performed immunohistochemical analyses of MxA and PKR in postmortem brains from 4 patients with GSS (P102L) and 5 patients with sCJD. Myxovirus resistance protein A and PKR showed astrocytic immunoreactivity in sCJD and GSS, although their distribution patterns differed. In GSS, astrocytes adjacent to PrP plaques exhibited strong MxA expression in somata and processes encircling plaques with greater positivity than in distant astrocytes. In contrast, PKR expression was confined to astrocyte somata. This differential localization indicates distinct functional contributions to astrocytic responses. These findings indicate that astrocytic MxA and PKR are direct type I IFN signaling targets; moreover, the close association of MxA with PrP plaques in GSS suggests involvement in plaque-associated astrocyte responses and highlights a possible protective function of astrocytes.

PMID:
42900709
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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