Nicotinic Receptors Present Potential Alzheimer's Disease Treatment Target

Inhibition of a subunit of the nicotinic receptor showed protective effects against amyloid beta peptide.

Scientists in a recent study identified nicotinic receptors as a new treatment target for Alzheimer’s disease, since previous studies show that nicotine can be beneficial for the memory.

Patients with Alzheimer’s disease have a build-up of amyloid plaques, which then leads to neurofibrillary degeneration, and the death of nerve cells. Once the plaques form, there is significant irreversible memory loss.

Alzheimer’s disease-related changes in the brain can begin as much as 10 years before symptoms appear, so identifying amyloid beta peptide while it is still soluble is important. In a study published in Neurobiology of Aging, scientists examined the effects of amyloid beta peptide build-up and nicotinic receptors, both located in the hippocampus region of the brain.

Nicotinic receptors locked in the cell membrane are sensitive to neurotransmitters, and allow for communication inside and outside the cell. The receptors are involved in nervous system functions, including memory.

There are 9 gene code nicotinic receptor subunits, and 4 of the subunits are involved in the process, according to the study. The researchers were able to determine the exact structure of the nicotinic receptors in the hippocampus, and focused on the β2 subunit of the receptor.

In a mouse model of Alzheimer’s disease, scientists blocked the gene coding for the β2 subunit, which suggests this approach can prevent memory loss, according to the study. The mice without β2 were protected from amyloid beta plaques, and did not develop Alzheimer’s disease-related memory loss.

The researchers believe their findings suggest the β2 subunit of the receptor is a target of soluble amyloid beta peptide.

“Characterizing this new therapeutic target will enable us to test molecules that are capable of blocking the β2 subunit,” said study lead author Uwe Maskos. “The aim is to find a therapeutic molecule that resembles nicotine but does not have the same harmful effects (dependence, premature cell aging, increased heart rate, effects on the gastroenteric system, etc).”