{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:58Z","timestamp":1790618278569,"version":"4.1.0"},"reference-count":81,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:00:00Z","timestamp":1788566400000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200775"],"award-info":[{"award-number":["32200775"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      P7C3 compounds are aminopropyl carbazole derivatives identified through phenotypic screening for proneurogenic activity. They directly activate nicotinamide phosphoribosyltransferase (NAMPT), the rate\u2010limiting enzyme in the NAD\n                      <jats:sup>+<\/jats:sup>\n                      salvage pathway. However, a comprehensive synthesis of their mechanisms and therapeutic potential across neurological disorders is currently lacking.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic literature review was conducted in PubMed, Web of Science, and Scopus to synthesize the discovery trajectory, structure\u2013activity relationships, molecular mechanisms, and preclinical efficacy of P7C3 compounds. The following keyword combinations were used: (\u201cP7C3\u201d OR \u201cP7C3 compound\u201d) AND (\u201cNAMPT\u201d OR \u201cNAD+\u201d OR \u201csirtuin\u201d OR \u201cmitochondria\u201d) AND (\u201cneuroprotection\u201d OR \u201cneurodegenerative\u201d).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      P7C3 elevates intracellular NAD\n                      <jats:sup>+<\/jats:sup>\n                      levels, engages SIRT1 and SIRT3 deacetylase cascades, enhances mitochondrial quality control and attenuates oxidative stress. This review discusses the discovery, structure\u2013activity relationships, and molecular mechanisms of P7C3, with a particular emphasis on mitochondrial dynamics and redox homeostasis. The efficacy of P7C3 in preclinical studies was evaluated across Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), ischemic stroke, depression, and chemotherapy\u2010induced neuropathy. These neuroprotective effects occur independently of disease\u2010specific aggregates. Challenges hindering clinical application include the on\u2010target safety of NAMPT activation given the concurrent development of NAMPT inhibitors for tumorigenesis, the absence of validated predictive biomarkers, and the failure of prior NAMPT\u2010targeting trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>P7C3 illustrates how phenotypic screening coupled with target deconvolution can yield therapeutic candidates with potential applications across a broad spectrum of neurological disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71139","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T07:01:22Z","timestamp":1788591682000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>P7C3<\/scp>\n                    Compounds as Targeted Mitochondrial Therapeutics for Brain Disorders"],"prefix":"10.1002","volume":"32","author":[{"given":"Yajing","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacy Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohuan","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Children's Hospital of Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwei","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Children's Hospital of Soochow University  Suzhou 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