Small-molecule Klotho enhancers as novel treatment of neurodegeneration


The majority of neurodegenerative diseases have an important age component, and thus, understanding the molecular changes that occur during normal aging of the brain is of utmost relevance. In search for the basis of the age-related cognitive decline found in humans, monkeys and rodents, we study the rhesus monkey. Surprisingly, there is no loss of neurons in aged monkey brains. However, we reported white matter and myelin abnormalities in aged monkeys, similar to those observed in Alzheimer’s disease and multiple sclerosis patients. In a microarray analysis comparing young and old monkey white matter, we discovered that Klotho is downregulated in the aged brain. We then asked whether there is a connection between the age-related cognitive decline, myelin abnormalities and Klotho downregulation. If such a connection is found, compounds that upregulate Klotho expression could become of therapeutic interest for the treatment of multiple sclerosis, and perhaps even Alzheimer’s disease.




Copyright 2012 Future Medicinal Chemistry. This is a post-print version of a published paper that is available at: Recommended ctiation: Abraham, Carmela R., CiDi Chen, Gregory D. Cuny, Marcie A. Glicksman, and Ella Zeldich. "Small-molecule Klotho enhancers as novel treatment of neurodegeneration." Future medicinal chemistry 4, no. 13 (2012): 1671-1679.. doi: 10.4155/fmc.12.134. This item has been deposited in accordance with publisher copyright and licensing terms and with the author's permission.