Stem Cell-Derived Exosomes As Neurotherapeutic Agents: Mechanisms of Immunomodulation and Neural Regeneration in Neurodegenerative Disorders

Neurodegenerative disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and ischemic stroke cause progressive and often irreversible neuronal loss, leading to major functional disability. Conventional pharmacological therapies primarily offer symptomatic relief and fail to promote neuro-restoration. Stem cell-derived exosomes have recently gained attention as acellular, regenerative biologics capable of modulating inflammation, enhancing synaptic repair, and facilitating neural recovery. These nanoscale vesicles carry bioactive molecules, including microRNAs (miRNAs) and growth factors, that replicate many of the paracrine benefits of stem cells without the associated risks of tumorigenicity or immune rejection. The objective of this review is to critically evaluate recent evidence on the neuroprotective, immunomodulatory, and translational mechanisms of stem cell-derived exosomes in major neurodegenerative and cerebrovascular disorders, highlighting their clinical relevance and therapeutic potential. Preclinical studies suggest that exosome administration may restore mitochondrial function, reduce oxidative stress, and support neuronal survival, with associated improvements in cognitive and motor outcomes in experimental models of AD, PD, and stroke. Exosomal miRNAs such as miR-21, miR-124, and miR-133b mediate neuroprotective effects through phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK), and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, while miR-146a promotes immunomodulation by suppressing pro-inflammatory cytokines and facilitating microglial repair phenotypes. Early-phase clinical studies primarily demonstrate feasibility and short-term safety, with exploratory signals of neurological improvement that require confirmation in adequately powered trials. Despite challenges in standardization and regulation, exosome-based therapy represents a scalable, safe, and clinically translatable strategy for neuro-regeneration, with significant promise for future management of brain network disorders.