Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Jan;58(1):281-303.
doi: 10.1007/s12035-020-02116-9. Epub 2020 Sep 15.

Multi-Target Drug Candidates for Multifactorial Alzheimer's Disease: AChE and NMDAR as Molecular Targets

Md Sahab Uddin  1   2 , Abdullah Al Mamun  3   4 , Md Tanvir Kabir  5 , Ghulam Md Ashraf  6   7 , May N Bin-Jumah  8 , Mohamed M Abdel-Daim  9   10
Affiliations
Review

Multi-Target Drug Candidates for Multifactorial Alzheimer's Disease: AChE and NMDAR as Molecular Targets

Md Sahab Uddin et al. Mol Neurobiol. 2021 Jan.

Abstract

Alzheimer's disease (AD) is one of the most common forms of dementia among elder people, which is a progressive neurodegenerative disease that results from a chronic loss of cognitive activities. It has been observed that AD is multifactorial, hence diverse pharmacological targets that could be followed for the treatment of AD. The Food and Drug Administration has approved two types of medications for AD treatment such as cholinesterase inhibitors (ChEIs) and N-methyl-D-aspartic acid receptor (NMDAR) antagonists. Rivastigmine, donepezil, and galantamine are the ChEIs that have been approved to treat AD. On the other hand, memantine is the only non-competitive NMDAR antagonist approved in AD treatment. As compared with placebo, it has been revealed through clinical studies that many single-target therapies are unsuccessful to treat multifactorial Alzheimer's symptoms or disease progression. Therefore, due to the complex nature of AD pathophysiology, diverse pharmacological targets can be hunted. In this article, based on the entwined link of acetylcholinesterase (AChE) and NMDAR, we represent several multifunctional compounds in the rational design of new potential AD medications. This review focus on the significance of privileged scaffolds in the generation of the multi-target lead compound for treating AD, investigating the idea and challenges of multi-target drug design. Furthermore, the most auspicious elementary units for designing as well as synthesizing hybrid drugs are demonstrated as pharmacological probes in the rational design of new potential AD therapeutics.

Keywords: AChE; Alzheimer’s disease; Multi-target drugs; Multi-target-directed ligands; NMDAR.

PubMed Disclaimer

References

    1. Sharma P, Sharma A, Fayaz F et al (2020) Biological signatures of Alzheimer’s disease. Curr Top Med Chem 20:770–781. https://doi.org/10.2174/1568026620666200228095553 - DOI - PubMed
    1. Uddin MS, Kabir MT, Tewari D et al (2020) Revisiting the role of brain and peripheral Aβ in the pathogenesis of Alzheimer’s disease. J Neurol Sci 416:116974. https://doi.org/10.1016/j.jns.2020.116974 - DOI - PubMed
    1. Selkoe DJ, Hardy J (2016) The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 8:595–608. https://doi.org/10.15252/emmm.201606210 - DOI - PubMed - PMC
    1. Uddin MS, Al Mamun A, Kabir MT et al (2019) Nootropic and anti-Alzheimer’s actions of medicinal plants: molecular insight into therapeutic potential to alleviate Alzheimer’s neuropathology. Mol Neurobiol 56:4925–4944. https://doi.org/10.1007/s12035-018-1420-2 - DOI - PubMed
    1. Mufson EJ, Counts SE, Perez SE, Ginsberg SD (2008) Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications. Expert Rev Neurother 8:1703–1718. https://doi.org/10.1586/14737175.8.11.1703 - DOI - PubMed - PMC

MeSH terms

Substances

LinkOut - more resources