Is Alzheimer’s Disease The Diabetes Of The Brain?

The drug memantine blocks improves symptoms of both diabetes and Alzheimer’s disease in mice by blocking a receptor called Kir6.2.

AsianScientist (Nov. 21, 2016) – Alzheimer’s and diabetes have something in common: they both respond to treatment with the drug memantine. These findings, by researchers at Tohoku University, have been published in Molecular Psychiatry.

Memantine, a drug widely used to treat Alzheimer’s disease, is a well known inhibitor of the N-methyl-D-aspartate (NMDA) receptors that prevent excessive glutamate transmission in the brain. Observing similarities in the way insulin signaling works in the brain and in the pancreas of diabetic patients, a team of researchers led by Dr. Shigei Moriguchi and Professor Kohji Fukunaga investigated the effect of memantine on Kir6.2, a glucose-sensing potassium channel highly expressed in the brain.

“In the pancreas, the Kir6.2 channel blockade increases insulin signaling, and insulin signaling decreases the blood glucose levels,” Moriguchi explained. “In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade.”

In their experiments with mice, the researchers found that memantine treatment improved impaired hippocampal long-term potentiation (LTP) and memory-related behaviors in the mice through the inhibition of ATP-sensitive potassium channel (KATP) Kir6.2.

“Since KATP channels Kir6.1 or Kir6.2 are critical components of sulfonylurea receptors which are downstream insulin receptor signaling, KATP channel inhibition by memantine mediates the anti-diabetic drug action in peripheral tissues,” Moriguchi said. “This leads to improved cognitive functions and improved memory retention among Alzheimer’s patients.”

The researchers now hope that results of their study and the parallels drawn with diabetes will lead to new treatments for Alzheimer’s disease through the inhibition of Kir6.2.


The article can be found at: Moriguchi et al. (2016) Blockade of the KATP Channel Kir6.2 by Memantine Represents a Novel Mechanism Relevant to Alzheimer’s Disease Therapy.

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Source: Tohoku University; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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