{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:22Z","timestamp":1787028502887,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AT10980"],"award-info":[{"award-number":["AT10980"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AG069229"],"award-info":[{"award-number":["AG069229"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1IK6 BX004982"],"award-info":[{"award-number":["1IK6 BX004982"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["AT10980"],"award-info":[{"award-number":["AT10980"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["AG069229"],"award-info":[{"award-number":["AG069229"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["1IK6 BX004982"],"award-info":[{"award-number":["1IK6 BX004982"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) is the second most common neurodegenerative disorder in human and loss-of-functions DJ-1 mutations are associated with a familial form of early onset PD. Functionally, DJ-1 (PARK7), a neuroprotective protein, is known to support mitochondria and protect cells from oxidative stress. Mechanisms and agents by which the level of DJ-1 could be increased in the CNS are poorly described. RNS60 is a bioactive aqueous solution created by exposing normal saline to Taylor-Couette-Poiseuille flow under high oxygen pressure. Recently we have described neuroprotective, immunomodulatory and promyelinogenic properties of RNS60. Here we delineate that RNS60 is also capable of increasing the level of DJ-1 in mouse MN9D neuronal cells and primary dopaminergic neurons, highlighting another new neuroprotective effect of RNS60. While investigating the mechanism we found the presence of cAMP response element (CRE) in DJ-1 gene promoter and stimulation of CREB activation in neuronal cells by RNS60. Accordingly, RNS60 treatment increased the recruitment of CREB to the DJ-1 gene promoter in neuronal cells. Interestingly, RNS60 treatment also induced the enrollment of CREB-binding protein (CBP), but not the other histone acetyl transferase p300, to the promoter of DJ-1 gene. Moreover, knockdown of CREB by siRNA led to the inhibition of RNS60-mediated DJ-1 upregulation, indicating an important role of CREB in DJ-1 upregulation by RNS60. Together, these results indicate that RNS60 upregulates DJ-1 in neuronal cells via CREB\u2013CBP pathway. It may be of benefit for PD and other neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms24054652","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T03:00:38Z","timestamp":1677553238000},"page":"4652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Upregulation of DJ-1 in Dopaminergic Neurons by a Physically-Modified Saline: Implications for Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"24","author":[{"given":"Malabendu","family":"Jana","sequence":"first","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridevi","family":"Dasarathy","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supurna","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Revalesio Corporation, Tacoma, WA 98421, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalipada","family":"Pahan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"},{"name":"Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson\u2019s disease: Mechanisms and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev.neuro.22.1.123","article-title":"Etiology and pathogenesis of Parkinson\u2019s disease","volume":"22","author":"Olanow","year":"1999","journal-title":"Annu. 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