Potential New Target for Alzheimer’s Disease Treatment

The research team has identified Keap1 (Kelch-like ECH-associated protein 1) as a possible new target for the development of drugs that can be used to prevent Alzheimer’s disease. Their research was published in PLOS Genetics.

Research on Alzheimer’s Disease

With a steady increase in the general life span of the population, the number of people suffering from age-related neurodegenerative diseases is likely to rise. This makes Alzheimer’s disease an important topic for research. The research team has discovered a possible molecular target for the development of drugs for Alzheimer’s disease called Keap1, based on their experiments on the fruit fly.

In order to understand how this new target will be useful in Alzheimer’s disease, we have to understand about a protein called Nrf2 (nuclear factor erythroid 2 [NF-E2]-related factor 2 [Nrf2]). Nrf2 activates cell protection genes, and therefore protects the brain cells from stressful conditions. The levels of Nrf2 are reduced in people suffering from Alzheimer’s disease. Therefore, theoretically, activators of Nrf2 could be beneficial in the treatment of Alzheimer’s disease. Unfortunately, such activators can also cause adverse effects due to over-activation of Nrf2.

Considering the above, the researchers explored a new method to activate Nrf2. They tried out the inhibition of another protein called Keap1. Keap1 is a negative regulator of Nrf2; therefore inhibition of Keap1 indirectly activates Nrf2 and could help to prevent the death of brain cells, and thereby keep Alzheimer’s and other neurodegenerative diseases at bay. The side effects will also hopefully be less than direct Nrf2 activators.

The research team also demonstrated that a compound that blocks the binding of Nrf2 and Keap1 could prevent damage to mouse nerve cells similar to that produced in Alzheimer’s disease.

The research is at an early stage. Further research on this novel target could see the development of a preventive medication for Alzheimer’s and other neurodegenerative diseases, which is the need of the hour.

Alzheimer’s Disease

Alzheimer’s disease is a brain disorder that develops in older genetically predisposed individuals. The connections between the brain cells are lost and the brain cells eventually die. Brain cells cannot regenerate, and therefore the damage cannot be reversed. Affected people suffer from memory loss, progressive cognitive decline, finally reaching a stage where they cannot recognize their close family and friends.

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Medications to treat Alzheimer’s disease mainly target the symptoms and improve the patient’s quality of life. Unfortunately, they provide only temporary relief and do not stop the progression of the condition. In addition, there are no medications available to prevent Alzheimer’s disease.

References:

1. Kerr F, Sofola-Adesakin O, Ivanov DK, Gatliff J, Gomez Perez-Nievas B, Bertrand HC, et al. (2017) Direct Keap1-Nrf2 disruption as a potential therapeutic target for Alzheimer’s disease. PLoS Genet 13(3): e1006593. doi:10.1371/journal.pgen.1006593
2. Alzheimer's Disease Information Page - (https://www.ninds.nih.gov/Disorders/All-Disorders/Alzheimers-Disease-Information-Page)

Source-Medindia