Extracellular Vesicles in Neurodegenerative Diseases: From Biomarker Discovery to Precision Therapeutics

Neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis, continue to present significant global health challenges due to their complex pathogenesis, progressive nature, and limited therapeutic options. In recent years, extracellular vesicles (EVs)—nanosized membrane-bound particles including exosomes and microvesicles—have emerged as key players in this field, revolutionizing our understanding of intercellular communication in the central nervous system. EVs naturally carry a rich cargo of bioactive molecules, including proteins, lipids, and nucleic acids, which they deliver to recipient cells. Their ability to cross the blood–brain barrier (BBB) and influence neuroinflammatory, neurodegenerative, and neuroregenerative pathways has propelled them to the forefront of neurological research. Crucially, EVs exhibit a dual role: they may contribute to disease pathogenesis by spreading pathological agents such as amyloid-beta (Aβ), tau, and α-synuclein, or, conversely, serve as protective agents capable of modulating immune responses, preserving BBB integrity, and promoting neuronal repair. Furthermore, their stability in circulation and presence in easily accessible biofluids like blood, urine, and cerebrospinal fluid make EVs ideal candidates for non-invasive biomarkers. Molecular profiling of EVs has revealed disease-specific cargo signatures—including altered microRNAs, phosphorylated tau, and inflammatory cytokines—that enable early diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. In the realm of therapeutics, engineered and stem-cell-derived EVs are being explored as novel delivery systems for neuroprotective agents, anti-inflammatory compounds, siRNA, and gene-editing tools. These EV-based platforms hold promise for precision medicine approaches, offering targeted delivery with reduced immunogenicity and enhanced biocompatibility.

This Special Issue invites cutting-edge research articles and comprehensive reviews focused on the mechanisms of EV biogenesis, cargo selection, and uptake within the nervous system; the role of EVs in neuroinflammation, synaptic plasticity, and neuronal degeneration; EV-based biomarker discovery for early diagnosis and disease monitoring; innovations in EV engineering for targeted drug and gene delivery; advances in scalable EV isolation, characterization, and standardization for clinical applications; and the development of personalized and patient-derived EV-based therapies in neurology. By bringing together multidisciplinary perspectives from neuroscience, molecular biology, clinical research, and nanotechnology, this Special Issue aims to illuminate the transformative potential of extracellular vesicles in diagnosing and treating neurodegenerative disorders and accelerate their translation into clinical practice.

Dr. Mangesh Dattu Hade
Guest Editor

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• neurodegenerative diseases
• extracellular vesicles
• Alzheimer's disease
• Parkinson's disease
• multiple sclerosis
• blood–brain barrier
• neuroinflammation
• biomarker discovery
• EV-based therapeutics
• precision medicine