Work

Targeting mitochondrial dysfunction to quell neuroinflammation in central nervous system (CNS): a new strategy for treating CNS disease with nanomedicines

Year: 2026

Type: article

Abstract: Neuroinflammation has emerged as an important pathogenic factor in central nervous system (CNS) disease, including various neurodegenerative diseases, brain injuries, and autoimmune conditions, affecting approximately 3 billion people worldwide. Mitochondrial dysfunction within neurovascular unit (NVU) cells not only initiates neuronal damage and blood-brain barrier (BBB) disruption but also critically reprograms immunometabolism, shifting microglia and infiltrating immune cells toward a pro-inflammatory, glycolysis-dominant state while impairing anti-inflammatory, oxidative phosphorylation-dependent functions. This metabolic rewiring fuels a vicious, self-amplifying cycle between mitochondrial impairment and sustained neuroinflammation. Consequently, targeting mitochondrial dysfunction has therefore emerged as a promising therapeutic strategy for controlling neuroinflammation. However, the double-membrane structure of mitochondria, coupled with the restrictive BBB, imposes formidable barriers to therapeutic delivery. Nanomedicine offers unprecedented opportunities. Advanced nanodrugs, engineered with mitochondrial-targeting ligands, stimuli-responsive materials, or biomimetic coatings, enable precise delivery of therapeutics directly to impaired mitochondria within the CNS. This review summarizes recent advances in mitochondrial dysfunction-induced neuroinflammation, highlights emerging nanotechnology-based mitochondrial targeting strategies in various CNS diseases, and discusses the existing challenges and future perspectives for translating these approaches into effective CNS therapies.

Source: 中国科学通报：英文版

DOI: 10.1016/j.scib.2026.05.020