Abstract: Microglia, the primary immune cells of the central nervous system (CNS), play essential roles in immune surveillance, synaptic pruning, and modulation of neuroinflammation. In neurodegenerative diseases such as Alzheimer’s disease, microglial dysfunction has been implicated in exacerbating disease progression. Chronic microglial activation results in the release of pro-inflammatory cytokines and neurotoxic factors, leading to neuronal damage and amplifying neuroinflammation. Understanding the dual roles of microglia in maintaining CNS health and contributing to disease processes offers critical insights for therapeutic development. To explore potential therapeutic strategies, we evaluated the functions of several genes involved in the clearance of misfolded proteins, such as amyloid-beta (Aβ) and the regulation of inflammation in induced pluripotent stem cell (iPSC)-derived microglia. Our study revealed that overexpression of interleukin-10 (IL-10), an anti-inflammatory cytokine, in iPSC-derived microglia not only suppressed inflammation but also enhanced Aβ clearance. This dual action represents a key mechanism for addressing neurodegenerative diseases characterized by Aβ accumulation and neuroinflammation. These findings highlight the therapeutic potential of IL-10-overexpressing iPSC-derived microglia as a promising platform for ex vivo gene therapy research targeting Alzheimer’s disease, other neurodegenerative conditions, and psychiatric disorders.
Funding Source: This research was supported by AMED under Grant Number JP24bm1323001h0102
