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One of the major sources contributing to the overall level of stress is the reactive oxygen species (ROS) generated by mitochondria. The driving force for ROS production is the proton gradient across the inner mitochondrial membrane. This gradient can be modulated by members of the uncoupling protein family, particularly the widely expressed UCP2. The overexpression and knockout studies of UCP2 in mice have established the ability of this protein to provide neuroprotection in a number of animal models of neurological disease, including retinal diseases. The expression and activity of UCP2 are controlled at the transcriptional, translational and post-translational levels, making it an ideal candidate for therapeutic intervention. In addition to regulation by a number of growth factors, including the neuroprotective factors LIF and PEDF, small molecule activators of UCP2 have been found to reduce mitochondrial ROS production and protect against cell death both in culture and animal models of retinal degeneration. Such studies point to the development of new therapeutics to combat a range of blinding retinal degenerative diseases and possibly other diseases in which oxidative stress plays a key role.<\/jats:p>","DOI":"10.3390\/ijms23105672","type":"journal-article","created":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T23:14:26Z","timestamp":1652915666000},"page":"5672","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases"],"prefix":"10.3390","volume":"23","author":[{"given":"Colin J.","family":"Barnstable","sequence":"first","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"},{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin 300384, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin 300384, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Tombran-Tink","sequence":"additional","affiliation":[{"name":"Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA"},{"name":"Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin 300384, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Hirschenson, J., Melgar-Bermudez, E., and Mailloux, R.J. 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