Is Alzheimer’s Disease a Diabetic Disorder of the Brain?

Summary: Researchers have discovered a possible new treatment for Alzheimer’s disease after noticing the way in which insulin signaling works in the brains and pancreas of diabetic patients.

Source: Tohoku University.

Researchers at Tohoku University have found a promising treatment for Alzheimer’s disease, by noticing a similarity in the way insulin signaling works in the brain and in the pancreas of diabetic patients.

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

The research group, led by Dr. Moriguchi and Professor Kohji Fukunaga of the Graduate School of Pharmaceutical Sciences, thus concluded that Alzheimer’s disease can be described as a diabetic disorder of the brain.

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. Researchers have now found that memantine also inhibits the ATP-sensitive potassium channel (Kir6.2 channel), improving insulin signal dysfunction in the brain.

In their experiment 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 KATP channel Kir6.2.

Image shows a schematic for the blockade of Kir6.

“Since KATP channels Kir6.1 or Kir6.2 are critical components of sulfonylurea receptors (SURs) which is downstream insulin receptor signaling, the KATP channel inhibition by Memantine mediates the anti-diabetic drug action in peripheral tissues,” says Dr. Moriguchi. “And 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, using the inhibition of Kir6.2 channel.

ABOUT THIS ALZHEIMER’S DISEASE RESEARCH ARTICLE

Source: Shigeki Moriguchi – Tohoku University
Image Source: NeuroscienceNews.com image is credited to Shigeki Moriguchi.
Original Research: Abstract for “Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy” by S Moriguchi, T Ishizuka, Y Yabuki, N Shioda, Y Sasaki, H Tagashira, H Yawo, J Z Yeh, H Sakagami, T Narahashi and K Fukunaga in Molecular Psychiatry. Published online October 25 2016 doi:10.1038/mp.2016.187

Tohoku University. “Is Alzheimer’s Disease a Diabetic Disorder of the Brain?.” NeuroscienceNews. NeuroscienceNews, 9 November 2016.
<http://neurosciencenews.com/insulin-alzheimers-diabetes-5464/&gt;.

Abstract

Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy

Here, we report a novel target of the drug memantine, ATP-sensitive K+ (KATP) channels, potentially relevant to memory improvement. We confirmed that memantine antagonizes memory impairment in Alzheimer’s model APP23 mice. Memantine increased CaMKII activity in the APP23 mouse hippocampus, and memantine-induced enhancement of hippocampal long-term potentiation (LTP) and CaMKII activity was totally abolished by treatment with pinacidil, a specific opener of KATP channels. Memantine also inhibited Kir6.1 and Kir6.2 KATP channels and elevated intracellular Ca2+ concentrations in neuro2A cells overexpressing Kir6.1 or Kir6.2. Kir6.2 was preferentially expressed at postsynaptic regions of hippocampal neurons, whereas Kir6.1 was predominant in dendrites and cell bodies of pyramidal neurons. Finally, we confirmed that Kir6.2 mutant mice exhibit severe memory deficits and impaired hippocampal LTP, impairments that cannot be rescued by memantine administration. Altogether, our studies show that memantine modulates Kir6.2 activity, and that the Kir6.2 channel is a novel target for therapeutics to improve memory impairment in Alzheimer disease patients.

“Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy” by S Moriguchi, T Ishizuka, Y Yabuki, N Shioda, Y Sasaki, H Tagashira, H Yawo, J Z Yeh, H Sakagami, T Narahashi and K Fukunaga in Molecular Psychiatry. Published online October 25 2016 doi:10.1038/mp.2016.187

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connie dello buono

Health educator, author and enterpreneur motherhealth@gmail.com or conniedbuono@gmail.com ; cell 408-854-1883 Helping families in the bay area by providing compassionate and live-in caregivers for homebound bay area seniors. Blogs at www.clubalthea.com Currently writing a self help and self cure ebook to help transform others in their journey to wellness, Healing within, transform inside and out. This is a compilation of topics Connie answered at quora.com and posts in this site.

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