{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:52:01Z","timestamp":1790614321806,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T00:00:00Z","timestamp":1628035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31601137"],"award-info":[{"award-number":["31601137"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601125"],"award-info":[{"award-number":["81601125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81673338"],"award-info":[{"award-number":["81673338"]}],"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":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The neurotropic growth factor PDGF\u2010BB was shown to have vital neurorestorative functions in various animal models of Parkinson's disease (PD). Previous studies indicated that the regenerative property of PDGF\u2010BB contributes to the increased intensity of tyrosine hydroxylase (TH) fibers in vivo. However, whether PDGF\u2010BB directly modulates the expression of TH, and the underlying mechanism is still unknown. We will carefully examine this in our current study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>MPTP\u2010lesion mice received PDGF\u2010BB treatment via intracerebroventricular (i.c.v) administration, and the expression of TH in different brain regions was assessed by RT\u2010PCR, Western blot, and immunohistochemistry staining. The molecular mechanisms of PDGF\u2010BB\u2010mediated TH upregulation were examined by RT\u2010PCR, Western blot, ChIP assay, luciferase reporter assay, and immunocytochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We validated a reversal expression of TH in MPTP\u2010lesion mice upon i.c.v administration of PDGF\u2010BB for seven days. Similar effects of PDGF\u2010BB\u2010mediated TH upregulation were also observed in MPP\n                      <jats:sup>+<\/jats:sup>\n                      \u2010treated primary neuronal culture and dopaminergic neuronal cell line SH\u2010SY5Y cells. We next demonstrated that PDGF\u2010BB rapidly activated the pro\u2010survival PI3K\/Akt and MAPK\/ERK signaling pathways, as well as the downstream CREB in SH\u2010SY5Y cells. We further confirmed the significant induction of p\u2010CREB in PDGF\u2010BB\u2010treated animals in vivo. Using a genetic approach, we demonstrated that the transcription factor CREB is critical for PDGF\u2010BB\u2010mediated TH expression. The activation and nucleus translocation of CREB were promoted in PDGF\u2010BB\u2010treated SH\u2010SY5Y cells, and the enrichment of CREB on the promoter region of TH gene was also increased upon PDGF\u2010BB treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our data demonstrated that PDGF\u2010BB directly regulated the expression of TH via activating the downstream Akt\/ERK\/CREB signaling pathways. Our finding will further support the therapeutic potential of PDGF\u2010BB in PD, and provide the possibility that targeting PDGF signaling can be harnessed as an adjunctive therapy in PD in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.13708","type":"journal-article","created":{"date-parts":[[2021,8,4]],"date-time":"2021-08-04T03:21:11Z","timestamp":1628047271000},"page":"1300-1312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Platelet\u2010derived growth factor (PDGF)\u2010BB protects dopaminergic neurons via activation of Akt\/ERK\/CREB pathways to upregulate tyrosine hydroxylase"],"prefix":"10.1111","volume":"27","author":[{"given":"Huan","family":"Chen","sequence":"first","affiliation":[{"name":"Institute of Neurology Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu Sichuan China"},{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-0954","authenticated-orcid":false,"given":"Yan","family":"Teng","sequence":"additional","affiliation":[{"name":"Institute of Neurology Sichuan Provincial People's Hospital University of Electronic Science and Technology of China  Chengdu Sichuan China"},{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingmin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine University of Electronic Science and Technology of China  Chengdu Sichuan 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