Project Summary: Neuroinflammation is a condition that can cause damage to the brain and lead to diseases like Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis. It is caused by inflammation in the central nervous system (CNS) and is linked to issues with mitochondria. Unfortunately, treating neuroinflammation is challenging due to the blood-brain barrier (BBB), which makes it difficult to deliver drugs to affected areas and target specific neuronal populations. Additionally, drugs that work for peripheral inflammation may not be as effective in the CNS due to its unique microenvironment and cellular interactions. Our team is exploring ways to reduce neuroinflammation using exosomes, which are small vesicles that can deliver molecules to recipient cells. We plan to use exosomes to deliver anti-inflammatory agents directly to the CNS, creating mitochondrial-targeting exosomes (MTEs) that carry anti-inflammatory microRNA (MTE-miRNA) to treat neuroinflammation. This method is expected to restore mitochondrial function, reduce oxidative stress, and modulate neuroinflammatory responses. MTE-miRNAs have the potential to revolutionize the treatment of neuroinflammatory disorders. To achieve this, we will prepare and evaluate MTEs containing microRNAs with anti-inflammatory properties, assess the impact of different dosages on reducing neuroinflammation in rats, and evaluate the effectiveness of MTE- miRNA treatments over different periods. Our primary outcomes are to improve mitochondrial function and inhibit inflammatory mediator production levels in rats with neuroinflammation. We will also gather crucial data on potential side effects and an appropriate treatment duration that balances efficacy and safety, informing future human studies. Another focus of this project is to train students extensively on exosome-based therapy and its potential use in treating neuroinflammation. Our educational goal is to equip students with the necessary knowledge and skills to make valuable contributions to biomedical research, and potentially create new and effective treatments for neuroinflammatory disorders.