Alzheimer's and Monepantel

Hi all, ( apologies a technical post)

Alzheimer's so research follows affects 6.2 million people in the USA. By 2050 that number is estimated to be 82 million.

Monepantel is a positive allosteric modulator of DEG3/DES2 type nicotinic acetylcholine receptors ( nACHRs).

Do the nAChRs mediate Ab induced tau pathology which are implicated in Alzheimer's.Dated research shows yes .

"A7 nicotinic acetylcholine receptor mediate B-Amyloid peptide induced tau protein phosphorylation. Wang 2003.

Loss of acetylcholine in the hippocampus and neocortex is closely associated with Alzheimer's disease.By restoring nicotinic acetylcholine receptors it would select targets for attenuating neurodegenerative
disease. Rationale is thus:

nAChRs promote the release of catecholamines stimulated by loss of acetylcholine AcH. These participate in the memory process of the interaction between the cerebral cortex and the hippocampus and consolidate memory.nAChRs regulate choline energy nerve pressure and effects nerve circuit function it also inhibits neuron excitability and negative feedback.

In 2024 we assume amyloid B plaque is the primary agent for tau hyperphosphorylation. Thus the main contributor to Alzheimer's pathogenesis.This is suggested by this study.

" Nicotinic acetylcholine receptors: Key targets for attenuating neurodegenerative disease. Bye et al 2023. They state :

Nicotinic acetylcholine receptors (nAChRs) are master regulators of immune functions via the cholinergic anti-inflammatory pathway and are expressed in microglia, the brain’s resident immune cells. There is an extensive dialogue between the neurons and the glial cells around them from which microglia are tasked with monitoring, nurturing, and defending their microenvironment. Dysregulation of any of these processes can have devastating and long-lasting consequences involving microglia-mediated neuroinflammation associated with neurodegenerative diseases such as Alzheimer’s disease.

A very brief overview of Monepantel and Alzheimer's.

Kpax