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In disease contexts, sEVs facilitate the intercellular dissemination of pathogenic proteins and nucleic acids, thereby contributing to the propagation of Alzheimer's disease (AD) and Parkinson's disease (PD) pathology. Conversely, their intrinsic biocompatibility, capacity to traverse brain barriers, and inherent organotropic properties position sEVs as highly promising nanocarriers for CNS drug delivery. While mesenchymal stem cell\u2013derived sEVs have been widely investigated in preclinical NDD models, accumulating evidence suggests that sEVs derived from neural cells, including neural stem cells, neurons, astrocytes, microglia, oligodendrocytes, and brain endothelial cells may offer superior brain targeting, disease relevance, and functional efficacy. This review provides a comprehensive and critical analysis of current knowledge on neural cell\u2013derived sEVs, encompassing their physiological roles in brain homeostasis, their involvement in AD and PD pathogenesis, and their emerging therapeutic applications. We discuss cell\u2010type\u2013specific sEV cargo profiles, mechanisms underlying blood\u2013brain and blood\u2013cerebrospinal fluid barrier traversal, and recent advances in endogenous and exogenous engineering strategies that enhance cargo loading, targeting precision, and therapeutic performance. Importantly, we address key translational challenges that currently limit clinical implementation. By integrating mechanistic insights with therapeutic and engineering perspectives, this review highlights neural cell\u2013derived sEVs as a biologically informed and versatile platform, underscoring their potential to advance next\u2010generation neuro\u2010nanomedicine for NDDs.<\/jats:p>","DOI":"10.1002\/adhm.202504608","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T09:21:23Z","timestamp":1775467283000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Small Extracellular Vesicles from Neural Cells: Physiological and Pathological Roles, and Potential in Neurodegenerative Therapy"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1543-9222","authenticated-orcid":false,"given":"Muhammad Waqas","family":"Salim","sequence":"first","affiliation":[{"name":"School of Natural Sciences Macquarie University  Sydney New South Wales 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