{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:06:34Z","timestamp":1785783994813,"version":"3.56.0"},"reference-count":115,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,19]],"date-time":"2019-07-19T00:00:00Z","timestamp":1563494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurodegenerative diseases are among the leading causes of mortality and disability worldwide. However, current therapeutic approaches have failed to reach significant results in their prevention and cure. Protein Kinase Cs (PKCs) are kinases involved in the pathophysiology of neurodegenerative diseases, such as Alzheimer\u2019s Disease (AD) and cerebral ischemia. Specifically \u03b5, \u03b4, and \u03b3PKC are associated with the endogenous mechanism of protection referred to as ischemic preconditioning (IPC). Existing modulators of PKCs, in particular of \u03b5PKC, such as \u03c8\u03b5Receptor for Activated C-Kinase (\u03c8\u03b5RACK) and Resveratrol, have been proposed as a potential therapeutic strategy for cerebrovascular and cognitive diseases. PKCs change in expression during aging, which likely suggests their association with IPC-induced reduction against ischemia and increase of neuronal loss occurring in senescent brain. This review describes the link between PKCs and cerebrovascular and cognitive disorders, and proposes PKCs modulators as innovative candidates for their treatment. We report original data showing \u03b5PKC reduction in levels and activity in the hippocampus of old compared to young rats and a reduction in the levels of \u03b4PKC and \u03b3PKC in old hippocampus, without a change in their activity. These data, integrated with other findings discussed in this review, demonstrate that PKCs modulators may have potential to restore age-related reduction of endogenous mechanisms of protection against neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms20143544","type":"journal-article","created":{"date-parts":[[2019,7,22]],"date-time":"2019-07-22T02:55:37Z","timestamp":1563764137000},"page":"3544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Age-Dependent Levels of Protein Kinase Cs in Brain: Reduction of Endogenous Mechanisms of Neuroprotection"],"prefix":"10.3390","volume":"20","author":[{"given":"Donatella","family":"Pastore","sequence":"first","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Pacifici","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunjan R.","family":"Dave","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Evelyn McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9401-7377","authenticated-orcid":false,"given":"Raffaele","family":"Palmirotta","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology, University of Bari \u201cAldo Moro\u201d, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Bellia","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Policlinico Tor Vergata Foundation, University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Pasquantonio","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiorella","family":"Guadagni","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2454-5940","authenticated-orcid":false,"given":"Giulia","family":"Donadel","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7671-0015","authenticated-orcid":false,"given":"Nicola","family":"Di Daniele","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Policlinico Tor Vergata Foundation, University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Abete","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples, Federico II, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Lauro","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Policlinico Tor Vergata Foundation, University Hospital, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Rundek","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Evelyn McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Perez-Pinzon","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Evelyn McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-5318","authenticated-orcid":false,"given":"David","family":"Della-Morte","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Neurology, The Evelyn McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL 33136, USA"},{"name":"Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1007\/s11515-011-1070-5","article-title":"The mechanism of protein kinase C regulation","volume":"6","author":"Kazi","year":"2011","journal-title":"Front. 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