{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T07:19:32Z","timestamp":1787901572305,"version":"build-2784847793"},"reference-count":34,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102314\u2010B\u2010371\u2010014"],"award-info":[{"award-number":["NSTC 113\u20102314\u2010B\u2010371\u2010014"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007632","name":"Changhua Christian Hospital","doi-asserted-by":"publisher","award":["111\u2010CCH\u2010HCR\u2010141"],"award-info":[{"award-number":["111\u2010CCH\u2010HCR\u2010141"]}],"id":[{"id":"10.13039\/501100007632","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mitochondrial dysfunction is a central pathogenic mechanism in Parkinson's disease (PD), particularly in genetic forms associated with respiratory chain impairment. Disease\u2010modifying therapies capable of restoring neuronal bioenergetics while achieving non\u2010invasive brain delivery remain lacking. This study investigated the therapeutic potential of an arginine\u2010enriched penetratin\u2010derived peptide (PenArg) in a genetic PD model carrying the\n                      <jats:italic>UQCRC1<\/jats:italic>\n                      (p.Tyr314Ser) mutation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The effects of PenArg labeled with 5\u2010FAM\u2013 or biotin were evaluated in\n                      <jats:italic>UQCRC1<\/jats:italic>\n                      knock\u2010in SH\u2010SY5Y cells and mice. Mitochondrial function, neuronal survival, and apoptosis were assessed using biochemical and imaging analyses. Brain distribution was evaluated 2\u2009h after intranasal administration, and therapeutic efficacy was examined following chronic intranasal treatment (three times weekly for six months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PenArg restored mitochondrial membrane potential, improved neuronal viability, and reduced oxidative stress\u2010induced apoptosis in cellular models. Imaging studies demonstrated partial mitochondrial localization in\u00a0vitro and in\u00a0vivo. Intranasal administration significantly improved locomotor performance, preserved dopaminergic neurons in the substantia nigra (SN) and striatum, and maintained hippocampal neuronal structure. Brain distribution analysis confirmed widespread brain penetration after intranasal administration. PenArg restored ATP synthase subunit beta expression and complex III activity while reducing cytochrome c release and caspase\u20103 activation in SN neurons. Treatment additionally attenuated skeletal muscle atrophy, enhanced antioxidant responses, and reduced circulating pro\u2010inflammatory cytokines.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PenArg confers neuroprotection through functional modulation of mitochondrial homeostasis and produces multisystem therapeutic benefits. Intranasal administration represents a non\u2010invasive strategy with disease\u2010modifying potential for mitochondrial\u2010related neurodegenerative disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71108","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:54:35Z","timestamp":1787745275000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Intranasal Administration of an Arginine\u2010Enriched Penetratin Peptide Confers Neuroprotection via Mitochondrial Functional Modulation in a Genetic Parkinson's Disease Model"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8349-862X","authenticated-orcid":false,"given":"Jui\u2010Chih","family":"Chang","sequence":"first","affiliation":[{"name":"Center of Regenerative Medicine and Tissue Repair Institute of ATP, Changhua Christian Hospital  Changhua 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