Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs
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Published version
Date
2020
Authors
Moos, Walter H.
Faller, Douglas V.
Glavas, Ioannis P.
Harpp, David N.
Kanara, Iphigenia
Mavrakis, Anastasios N.
Pernokas, Julie
Pernokas, Mark
Pinkert, Carl A.
Powers, Whitney R.
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OA Version
Published version
Citation
Walter H Moos, Douglas V Faller, Ioannis P Glavas, David N Harpp, Iphigenia Kanara, Anastasios N Mavrakis, Julie Pernokas, Mark Pernokas, Carl A Pinkert, Whitney R Powers, Konstantina Sampani, Kosta Steliou, Demetrios G Vavvas, Robert J Zamboni, Krishna Kodukula, Xiaohong Chen. 2020. "Klotho pathways, myelination disorders, neurodegenerative diseases, and epigenetic drugs." Biores Open Access, Volume 9, Issue 1, pp. 94 - 105. https://doi.org/10.1089/biores.2020.0004
Abstract
In this review we outline a rationale for identifying neuroprotectants aimed at inducing endogenous Klotho activity and expression, which is epigenetic action, by definition. Such an approach should promote remyelination and/or stimulate myelin repair by acting on mitochondrial function, thereby heralding a life-saving path forward for patients suffering from neuroinflammatory diseases. Disorders of myelin in the nervous system damage the transmission of signals, resulting in loss of vision, motion, sensation, and other functions depending on the affected nerves, currently with no effective treatment. Klotho genes and their single-pass transmembrane Klotho proteins are powerful governors of the threads of life and death, true to the origin of their name, Fates, in Greek mythology. Among its many important functions, Klotho is an obligatory co-receptor that binds, activates, and/or potentiates critical fibroblast growth factor activity. Since the discovery of Klotho a little over two decades ago, it has become ever more apparent that when Klotho pathways go awry, oxidative stress and mitochondrial dysfunction take over, and age-related chronic disorders are likely to follow. The physiological consequences can be wide ranging, potentially wreaking havoc on the brain, eye, kidney, muscle, and more. Central nervous system disorders, neurodegenerative in nature, and especially those affecting the myelin sheath, represent worthy targets for advancing therapies that act upon Klotho pathways. Current drugs for these diseases, even therapeutics that are disease modifying rather than treating only the symptoms, leave much room for improvement. It is thus no wonder that this topic has caught the attention of biomedical researchers around the world.
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Copyright Walter H. Moos et al. 2020; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.