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<front>
<journal-meta>
<journal-id journal-id-type="doi">10.1111/(ISSN)1471-4159</journal-id>
<journal-id journal-id-type="publisher-id">JNC</journal-id>
<journal-title-group>
<journal-title xml:lang="en">Journal of Neurochemistry</journal-title>
<abbrev-journal-title abbrev-type="publisher" xml:lang="en">J Neurochem</abbrev-journal-title>
</journal-title-group>
<issn publication-format="ppub">0022-3042</issn>
<issn publication-format="epub">1471-4159</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.1111/jnc.70170</article-id>
<article-id pub-id-type="publisher-id">JNC70170</article-id>
<article-id pub-id-type="society-id">JNC-2025-0328.R1</article-id>
<article-categories>
<subj-group subj-group-type="overline" xml:lang="en">
<subject>REVIEW</subject>
</subj-group>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>REVIEW</subject>
<subj-group subj-group-type="heading" xml:lang="en">
<subject>Special Issue: Extracellular Vesicles in Neurodegeneration and Neuroinflammation</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title xml:lang="en">Neural Stem Cell‐Derived Extracellular Vesicles for Advanced Neural Repair</article-title>
</title-group>
<contrib-group>
<contrib id="jnc70170-cr-0001" contrib-type="author">
<name>
<surname>Moretti</surname>
<given-names>Eduardo H.</given-names>
</name>
<xref ref-type="aff" rid="jnc70170-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="jnc70170-cr-0002" contrib-type="author">
<name>
<surname>Lin</surname>
<given-names>Ally L. Y.</given-names>
</name>
<xref ref-type="aff" rid="jnc70170-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="jnc70170-cr-0003" contrib-type="author">
<name>
<surname>Peruzzotti‐Jametti</surname>
<given-names>Luca</given-names>
</name>
<xref ref-type="aff" rid="jnc70170-aff-0001">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="jnc70170-aff-0002">
<sup>2</sup>
</xref>
</contrib>
<contrib id="jnc70170-cr-0004" contrib-type="author" corresp="yes">
<name>
<surname>Pluchino</surname>
<given-names>Stefano</given-names>
</name>
<email>spp24@cam.ac.uk</email>
<xref ref-type="corresp" rid="correspondenceTo">*</xref>
<xref ref-type="aff" rid="jnc70170-aff-0001">
<sup>1</sup>
</xref>
</contrib>
<contrib id="jnc70170-cr-0005" contrib-type="author" corresp="yes">
<name>
<surname>Mozafari</surname>
<given-names>Sabah</given-names>
</name>
<contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8166-2465</contrib-id>
<email>sm3010@cam.ac.uk</email>
<xref ref-type="corresp" rid="correspondenceTo">*</xref>
<xref ref-type="aff" rid="jnc70170-aff-0001">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="jnc70170-aff-0001">
<label>
<sup>1</sup>
</label>

<named-content content-type="organisation-division">Department of Clinical Neurosciences, National Institute for Health Research (NIHR) Biomedical Research Centre</named-content>

<institution>University of Cambridge</institution>

<city>Cambridge</city>
 <country country="GB">UK</country>

</aff>
<aff id="jnc70170-aff-0002">
<label>
<sup>2</sup>
</label>

<named-content content-type="organisation-division">Department of Metabolism, Digestion and Reproduction</named-content>

<institution>Imperial College London</institution>

<city>London</city>
 <country country="GB">UK</country>

</aff>
<author-notes>
<corresp id="correspondenceTo"><label>*</label>


<bold>Correspondence:</bold>
<break/>
Stefano Pluchino (<email>spp24@cam.ac.uk</email>)<break/>
Sabah Mozafari (<email>sm3010@cam.ac.uk</email>)<break/>

</corresp>
</author-notes>
<pub-date date-type="pub" publication-format="electronic"><day>30</day>
<month>07</month>
<year>2025</year>
</pub-date><pub-date date-type="pub" publication-format="print"><month>08</month>
<year>2025</year>
</pub-date><volume>169</volume>
<issue seq="320">8</issue>
<issue-id pub-id-type="doi">10.1111/jnc.v169.8</issue-id>
<elocation-id>e70170</elocation-id>
<history>

<date date-type="rev-recd">
<day>07</day>
<month>07</month>
<year>2025</year>
</date>

<date date-type="received">
<day>17</day>
<month>04</month>
<year>2025</year>
</date>

<date date-type="accepted">
<day>09</day>
<month>07</month>
<year>2025</year>
</date>

</history>
<permissions>
<copyright-statement content-type="issue-copyright">Copyright © 2025 International Society for Neurochemistry</copyright-statement>
<copyright-statement content-type="article-copyright">© 2025 The Author(s). <italic>Journal of Neurochemistry</italic> published by John Wiley &amp; Sons Ltd on behalf of International Society for Neurochemistry.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>© 2025 The Author(s). Journal of Neurochemistry published by John Wiley &amp; Sons Ltd on behalf of International Society for Neurochemistry.</copyright-holder>
<license>
<ali:license_ref>http://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open access article under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution</ext-link> License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract xml:lang="en" abstract-type="main">
<title>ABSTRACT</title>
<p xml:lang="en">The limited regenerative capacity of the central nervous system (CNS) severely hinders treatment of neurodegenerative and neuroinflammatory diseases. These conditions, frequently exacerbated by aging, share common hallmarks such as neuroinflammation, demyelination, and neuronal loss. While neural stem cells (NSCs) hold great therapeutic promise due to their paracrine effects, including extracellular vesicle (EV) release, direct transplantation presents significant challenges. This review focuses on NSC‐derived EVs as a novel therapeutic strategy, as we explore their multimodal mechanisms in modulating neuroinflammation, promoting neurogenesis, and restoring cellular bioenergetics through the delivery of bioactive molecules and mitochondrial transfer. Recent advances in NSC‐EV‐based therapies for age‐associated neurodegenerative diseases are highlighted, along with key challenges in EV production, preservation, and targeted delivery. Finally, we outline future directions for translating this promising approach into effective clinical treatments.</p>
<p xml:lang="en">

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<alt-text>image</alt-text>
</graphic>
</boxed-text>

</p>
</abstract>
<kwd-group kwd-group-type="author-generated" xml:lang="en">
<kwd id="jnc70170-kwd-0001">extracellular vesicles (EVs)</kwd>
<kwd id="jnc70170-kwd-0002">neural stem cells (NSCs)</kwd>
<kwd id="jnc70170-kwd-0003">neurodegeneration</kwd>
<kwd id="jnc70170-kwd-0004">neuroinflammation</kwd>
<kwd id="jnc70170-kwd-0005">regenerative neuroimmunology</kwd>
</kwd-group>
<funding-group>
<award-group id="funding-0001">
<funding-source>

<institution-wrap>
<institution>Bascule Charitable Trust</institution>
</institution-wrap>

</funding-source>
<award-id>RG98181</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0002">
<funding-source>

<institution-wrap>
<institution>Fondazione Italiana Sclerosi Multipla FIMS</institution>
</institution-wrap>

</funding-source>
<award-id>2018/R/14</award-id>
<award-id>2022/R‐Single/011</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0003">
<funding-source>

<institution-wrap>
<institution>Ferblanc Foundation</institution>
</institution-wrap>

</funding-source>
<award-id>G112716</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0004">
<funding-source>

<institution-wrap>
<institution>National MS Society Research Grant RG</institution>
</institution-wrap>

</funding-source>
<award-id>1802‐30200</award-id>
<award-id>RFA‐2203‐39318</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0005">
<funding-source>

<institution-wrap>
<institution>Fundação de Amparo à Pesquisa do Estado de São Paulo</institution>
<institution-id institution-id-type="doi">10.13039/501100001807</institution-id>
</institution-wrap>

</funding-source>
<award-id>2020/09399‐7</award-id>
<award-id>2023/14912‐3</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0006">
<funding-source>

<institution-wrap>
<institution>MRC Clinician Scientist Fellowship (CSF)</institution>
</institution-wrap>

</funding-source>
<award-id>APP25212</award-id>
</award-group>
</funding-group>
<funding-group>
<award-group id="funding-0007">
<funding-source>

<institution-wrap>
<institution>Evelyn Trust Grant Project</institution>
</institution-wrap>

</funding-source>
<award-id>24/08 Med‐24‐2313</award-id>
</award-group>
</funding-group>
<counts>
<fig-count count="4"/>
<table-count count="4"/>
<page-count count="25"/>
<word-count count="19500"/>
</counts>
</article-meta>
</front>
</article>