Identification of a Factor Promoting the Formation of Pathogenic Tau Aggregates and Neuronal Survival in Alzheimer's Disease_篮球比分直播

総務課
Tue, 23 Dec 2025 05:08:50 +0000
Research results

Alzheimer's disease (AD) is a progressive disease characterized by neuronal cell death, brain atrophy, and memory impairment. Tau aggregates, formed by the abnormal aggregation of Tau protein, play a crucial role in its pathogenesis. A research group led by Associate Professor TAKAHASHI Masahiko and Professor Emeritus FUJII Masahiro of the Department of Virology, Graduate School of Medical and Dental Sciences, Niigata University, focused on the protein USP10 (ubiquitin-specific protease 10), contained within Tau aggregates. In an AD model mouse expressing Tau protein, reducing USP10 expression suppressed Tau protein aggregation and mitigated AD progression. In patients with advanced, late-stage AD, USP10 expression levels decreased with Tau aggregation, suggesting that this promotes neuronal cell death. Increased neuronal cell death was also observed in mice lacking USP10 in the nervous system. These findings suggest that USP10 exerts different actions depending on the stage of AD. Specifically, maintaining USP10 expression promotes Tau aggregation in early-stage AD, whereas decreased USP10 expression accelerates neuronal cell death in late-stage AD.

This research was published in the scientific journal Molecular and Cellular Biology on December 8, 2025.

Key points

In early-stage AD model mice, USP10 increases Tau protein levels and promotes Tau aggregation.

In late-stage AD patients, decreased USP10 expression correlates with increased neuronal death.

Brain-specific USP10 knockout mice exhibit increased neuronal cell death.

USP10 promotes Tau aggregation and neuronal cell survival.

USP10 is suggested as a promising novel therapeutic target for AD.

Publication Details

Journal: Molecular and Cellular Biology
Title:Dual Regulatory Roles of USP10 in Tau Pathology and Neuronal Fate During Alzheimer’s Disease Progression
Authors:Masahiko Takahashi, Hiroki Kitaura, Asa Nakahara, Akiyoshi Kakita, Keisuke Watanabe, Taichi Kakihana, Toshifumi Hara, Yoshinori Katsuragi, Manami Yoshita-Takahashi, Sergei Anisimov, Takayuki Abe, Masahiro Fujii
Doi: 10.1080/10985549.2025.2575950