2026-04-16 理化学研究所
iPaDによる神経幹細胞の若返りとアルツハイマー病病態の改善
＜関連情報＞
- https://www.riken.jp/press/2026/20260416_1/index.html
- https://www.cell.com/cell-reports/fulltext/S2211-1247(26)00328-1
神経新生の活性化は、アルツハイマー病モデルマウスにおいてAMPキナーゼシグナル伝達を介してアミロイドβ病理と認知機能を改善する Activation of neurogenesis improves amyloid-β pathology and cognitive function through AMP kinase signaling in Alzheimer’s disease model mice
Masahiro Fukui ∙ Takashi Kaise ∙ Taimu Masaki ∙ Tyler Sakamoto ∙ Ryoichiro Kageyama
Cell Reports Published:April 9, 2026
DOI:https://doi.org/10.1016/j.celrep.2026.117250
Highlights
- iPaD treatment ameliorates Alzheimer’s disease pathology in model mice
- Prkag2 is upregulated in Alzheimer’s disease model mice and downregulated by iPaD
- Prkag2 knockdown ameliorates Alzheimer’s disease pathology in model mice
Summary
Adult hippocampal neurogenesis declines with aging and in neurological disorders, leading to cognitive impairment. We previously showed that inducing Plagl2 and antagonizing Dyrk1a (iPaD) rejuvenates aged neural stem cells (NSCs), enhancing neurogenesis and cognition in aged mice. Here, we found that NSC-specific iPaD treatment activates neurogenesis, reduces amyloid-β deposition, and improves cognition in Alzheimer’s disease model mice. Transcriptomic analysis revealed widespread changes in gene expression in the hippocampus after iPaD treatment. The upregulated genes include those associated with astrocyte and microglial activation involved in amyloid-β clearance, while several genes upregulated in Alzheimer’s disease are downregulated. Among the latter genes, knockdown of Prkag2 in the hippocampus most effectively enhances neurogenesis and reduces amyloid-β accumulation. Notably, both iPaD treatment and Prkag2 knockdown activate AMP-activated protein kinase signaling, upregulating genes involved in autophagy and cellular homeostasis. These results suggest that Prkag2 may represent a promising therapeutic target for neurodegenerative diseases, including Alzheimer’s disease.
