Abstract
The amyloid precursor protein (APP), presenilin 1 (PS1), amyloid beta (Aβ), and GSK3 are the effectors, which are significantly associated with progression of Alzheimer’s Disease (AD) and its symptoms. A significant protein, acetylcholinesterase (AChE) becomes dysfunctional as a result of cholinergic neuronal loss in AD pathology. However, certain associated peptides potentiate the release of primary neuropathological hallmarks, i.e., senile plaque and neurofibrillary tangles (NFTs), by modulating the alpha 7 acetylcholinesterase receptor (α7nAChR). The AChE variants, T30 and T14 have also been found to be elevated in AD patients and mimic the toxic actions of pathological events in patients. The manuscript discusses the significance of AChE inhibitors in AD therapeutics, by indicating the disastrous role of molecular alterations and elevation of AChE, accompanied with the downstream effects instigated by the peptide, supported by clinical evidence and investigations. The cyclized variant of AChE peptide, NBP14 has been identified as a novel candidate that reverses the harmful effects of T30, T14 and Aβ, mainly calcium influx, cell viability and AChE release. The review aims to grab the attention of neuro-researchers towards the significance of triggering effectors in propagating AD and role of AChE in regulating them, which can potentially ace the development of reliable therapeutic candidates, similar to NBP14, to mitigate neurodegeneration.
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•Molecular alterations in AChE peptide and its AD-like effects establish a connection between the peptide and pathology.•Elevated variants and downstream consequences: inter-relationship between AChE, P-Tau, GSK-3β, Aβ and PS1.•AChE inhibition as a potential therapeutic prospect and NBP14, an antagonistic novel cyclized variant.•Comparative analysis of NBP14 and a conventional drug in AD.