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<p>Neurodevelopmental disorders (NDDs), including autism spectrum disorders, attention-deficit hyperactivity disorders, schizophrenia, bipolar disorders, and other neurological disorders, present significant diagnostic and therapeutic challenges due to complex pathological physiology and heterogeneous presentation. Brain-derived exosomes, which are extracellular vesicles measuring 30–150&#xa0;nm, cross the blood–brain barrier, transporting disease-specific molecular cargoes such as proteins, lipids, and nucleic acids, making them promising biomarkers and therapeutic vehicles. Recent advances have identified exosomal features specific to the disorder, including a reduction in brain-derived neurotrophic factors and an increase in miR-125b in ADHD, an increase in miR-146a and IL-6 in autism spectrum disorders, a change in sphingolipid profiles in schizophrenia, and a dysregulation of phosphatidylserine in bipolar disorders. These molecular signatures enable noninvasive surveillance of disease progression and response. BDEs exhibit context-dependent functions and can be both neuroprotective and potential agents for disease spread, depending on the cellular microenvironment. Important translational barriers include standardizing isolation methods, scaling up clinical production, and developing regulatory frameworks. Current evidence supports progress in clinical trials and continues to investigate manufacturing standards and therapeutic dosage protocols for these agents. Brain-derived exosome represents a convergence of neuroscience and precision medicine, providing pathways for improving the diagnosis and customized treatment strategies for NDD.</p>

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Brain-Derived Exosomes in Neurodevelopmental and Neuropsychiatric Disorders: Molecular Insights, Therapeutic Potential, and Translational Challenges

  • 期刊论文

  • 发表日期：

    2025年8月2日

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  • Masoud Nikanfar,
  • Cigir Biray Avci,
  • Asghar Khalilnezhad,
  • Elham Shahriyari,
  • Alireza Nourazarian

摘要

Neurodevelopmental disorders (NDDs), including autism spectrum disorders, attention-deficit hyperactivity disorders, schizophrenia, bipolar disorders, and other neurological disorders, present significant diagnostic and therapeutic challenges due to complex pathological physiology and heterogeneous presentation. Brain-derived exosomes, which are extracellular vesicles measuring 30–150 nm, cross the blood–brain barrier, transporting disease-specific molecular cargoes such as proteins, lipids, and nucleic acids, making them promising biomarkers and therapeutic vehicles. Recent advances have identified exosomal features specific to the disorder, including a reduction in brain-derived neurotrophic factors and an increase in miR-125b in ADHD, an increase in miR-146a and IL-6 in autism spectrum disorders, a change in sphingolipid profiles in schizophrenia, and a dysregulation of phosphatidylserine in bipolar disorders. These molecular signatures enable noninvasive surveillance of disease progression and response. BDEs exhibit context-dependent functions and can be both neuroprotective and potential agents for disease spread, depending on the cellular microenvironment. Important translational barriers include standardizing isolation methods, scaling up clinical production, and developing regulatory frameworks. Current evidence supports progress in clinical trials and continues to investigate manufacturing standards and therapeutic dosage protocols for these agents. Brain-derived exosome represents a convergence of neuroscience and precision medicine, providing pathways for improving the diagnosis and customized treatment strategies for NDD.