An insight into structure-activity relationship of naturally derived biological macromolecules for the treatment of Alzheimer’s disease: a review

Abstract

Alzheimer’s disease (AD) is a neurological disorder that affects millions of people worldwide. There are currently no cures for AD, although various drugs are used to manage the symptoms and reduce the disease’s progression. AChE inhibitors such as rivastigmine, donepezil, galantamine, and the NMDA glutamate receptor antagonist memantine are currently FDA-approved drugs used in the treatment of AD. Recently, naturally derived biological macromolecules have shown promising results in the treatment of AD. Several biological macromolecules derived from natural sources are in various stages of preclinical and clinical trials. During the literature search, it was observed that there is a lack of a comprehensive review that particularly focuses on the role of naturally derived biological macromolecules (protein, carbohydrates, lipids, and nucleic acids) in the treatment of AD and the structure-activity relationship (SAR) approach for understanding the medicinal chemistry perspective. This review focuses on the SAR and probable mechanisms of action of biological macromolecules derived from natural sources for the treatment of AD, including peptides, proteins, enzymes, and polysaccharides. The paper further addresses the therapeutic possibilities of monoclonal antibodies, enzymes, and vaccines for the treatment of AD. Overall, the review provides insight into the SAR of naturally derived biological macromolecules in the treatment of AD. The ongoing research in this field holds great promise for the future development of AD treatment and provides hope for individuals affected by this devastating disease.

Communicated by Ramaswamy H. Sarma

Keywords:

• Alzheimer’s disease
• macromolecules
• AChE inhibitors
• protein
• carbohydrates
• nucleic acid
• SAR

Acknowledgments

The author, Subham Das, wishes to thank the Manipal Academy of Higher Education (MAHE), Manipal, for awarding him the Dr. T.M.A. Pai Doctoral fellowship. The authors also acknowledge the Manipal College of Pharmaceutical Sciences for providing facilities for this work. The authors also thank ChemDraw and BioRender.com.

Authors’ contributions

Debojyoti Halder: Conceptualization, analysis and interpretation of data, original draft preparation; Subham Das: Conceptualization, analysis and interpretation of data, original draft preparation, revised the manuscript, supervision; Alex Joseph: Interpretation of data, original draft writing and supervision.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Data sharing is not applicable—no new data is generated.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.