Through observing similarity in the way insulin signaling works in the brain and in the pancreas of diabetic patients, researchers at Tohoku University have found what may be a promising treatment for Alzheimer’s disease.
Led by Dr. Shigeki Moriguchi and Professor Kohji Fukunaga, the team says that Alzheimer’s disease can be described as a diabetic disorder of the brain.
“In the pancreas, the Kir6.2 channel blockade increases the insulin signaling, and insulin signaling decreases the blood glucose levels,” says Dr. Moriguchi. “In the brain, insulin signaling increases the acquisition of memory through CaM kinase II activation by Kir6.2 channel blockade."
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.
Improved Cognitive Functions
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.
“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.
S Moriguchi et al Blockade of the KATP channel Kir6.2 by memantine represents a novel mechanism relevant to Alzheimer’s disease therapy Molecular Psychiatry (2016). DOI: 10.1038/mp.2016.187
Image: Proposed model for blockade of Kir6.1 or Kir6.2 by memantine in hippocampus. Credit: Shigeki Moriguchi