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Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits and neuronal loss. Deposition of beta-amyloid peptide (A?) causes neurotoxicity through the formation of plaques in brains of Alzheimer's disease. Numerous studies have indicated that the neuropeptides including ghrelin, neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y, substance P and orexin are closely related to the pathophysiology of Alzheimer's disease. The levels of neuropeptides and their receptors change in Alzheimer's disease. These neuropeptides exert neuroprotective roles mainly through preventing A? accumulation, increasing neuronal glucose transport, increasing the production of neurotrophins, inhibiting endoplasmic reticulum stress and autophagy, modulating potassium channel activity and hippocampal long-term potentiation. Therefore, the neuropeptides may function as potential drug targets in the prevention and cure of Alzheimer's disease.

SUBMITTER: Chen XY

PROVIDER: S-EPMC6336706 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease.

Chen Xin-Yi XY Du Yi-Feng YF Chen Lei L

Frontiers in molecular neuroscience 20190111

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive deficits and neuronal loss. Deposition of beta-amyloid peptide (Aβ) causes neurotoxicity through the formation of plaques in brains of Alzheimer's disease. Numerous studies have indicated that the neuropeptides including ghrelin, neurotensin, pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y, substance P and orexin are closely related to the pathophysiology of Alzheimer's dis ...[more]

PMID: 30687008

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Project description:BACKGROUND:Alzheimer's disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (A?) protein. A? is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme 'transmembrane aspartyl protease, ?-secretase'. Inhibition of ?-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with A? peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, ?-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD. RESULTS:Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets. CONCLUSION:These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered.

Dataset Information

Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease.

Publications

Neuropeptides Exert Neuroprotective Effects in Alzheimer's Disease.

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