{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:48:06Z","timestamp":1789015686198,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Spinocerebellar ataxia type 3 (SCA3), the most common inherited ataxia, lacks effective therapies. Current microRNA (miRNA) approaches directly targeting\n                    <jats:italic>ataxin\u20103<\/jats:italic>\n                    (\n                    <jats:italic>ATXN3<\/jats:italic>\n                    ) mRNA risk reducing essential wild\u2010type ATXN3, a key regulator of proteostasis and various signaling pathways. Consequently, developing neuron\u2010targeted, noninvasive miRNA delivery strategies that employ alternative mechanisms is critical for SCA3. In this study, we engineered rabies virus glycoprotein (RVG)\u2010modified exosomes to deliver miR\u2010370 inhibitors to the brains of SCA3 mice, thereby upregulating the molecular chaperone DnaJ homolog subfamily B member 1 (DNAJB1) to promote clearance of mutant ATXN3. Systemic administration of RVG\u2010exosomes carrying miR\u2010370 inhibitors led to increased DNAJB1 expression, reduced mutant ATXN3 aggregation, improved neuronal survival, and restored motor coordination in SCA3 mice. Furthermore, combining miR\u2010370 inhibitors with miR\u201025\u2014a miRNA that directly targets\n                    <jats:italic>ATXN3<\/jats:italic>\n                    mRNA\u2014synergistically enhanced the reduction of pathogenic ATXN3 and provided greater neuroprotection compared to either therapy alone. These findings support the use of RVG\u2010exosome\u2010mediated miR\u2010370 inhibition as a noninvasive strategy to improve proteostasis in SCA3 and demonstrate its potential in combination with\n                    <jats:italic>ATXN3<\/jats:italic>\n                    mRNA\u2010targeting miRNAs, offering a promising therapeutic paradigm for SCA3 and similar neurodegenerative disorders.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601357rr","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T10:10:36Z","timestamp":1780913436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Engineered Exosomes Deliver\n                    <scp>miR<\/scp>\n                    \u2010370 Inhibitor to Regulate\n                    <scp>DNAJB1<\/scp>\n                    and Synergize With\n                    <scp>miR<\/scp>\n                    \u201025 in Improving\n                    <scp>SCA3<\/scp>\n                    Mice Behavior and Neuropathology"],"prefix":"10.1096","volume":"40","author":[{"given":"Ziyi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology, the Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Medical Research Center for Stroke Prevention and Treatment of Hunan Province, Department of Neurology, the Second Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics, Xiangya Hospital Central South University  Changsha China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixia","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurology, the Second Xiangya Hospital Central South University  Changsha China"},{"name":"Clinical Medical Research Center for Stroke Prevention 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