Research: Klotho

 Abraham CR, Chen C, Cuny GD, Glicksman MA, Zeldich E. Small-molecule Klotho enhancers as novel treatment of neurodegeneration. Future Med Chem. 2012;4:1671-9.

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. If there is a connection between  the age-related cognitive decline, myelin abnormalities and Klotho downregulation., compounds that upregulate Klotho expression could become of therapeutic interest for the treatment of multiple sclerosis, and perhaps even Alzheimer's disease.

Klotho is a transmembrane protein that, in addition to other effects, provides some control over the sensitivity of the organism to insulin and appears to be involved in aging. Using microarraywhich is  is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate (usually a glass slide or silicon thin-film cell) that assays large amounts of biological material using high-throughput screening methods. This study show that Klotho levels are reduced as we get older. This may be a therapeutic target for the future but at the moment it is largely science fantasy

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