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Vitamin-Based Derivatives for the Management of Alzheimer’s Disease

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Natural Product-based Synthetic Drug Molecules in Alzheimer's Disease

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Abstract

Vitamins are organic compounds; they help in the regulation of many bodily functions like cell proliferation and differentiation, immunological response, and metabolism. A deficiency of these molecules can cause severe medical conditions, i.e., beriberi, xerophthalmia, scurvy, Crohn’s disease, and others. Furthermore, studies have shown that vitamin deficiency might lead to many neuronal dysfunctions, even hampering the growth of neurons. This chapter explores the role of vitamins and their derivatives in the pathology of Alzheimer’s disease. Alzheimer’s disease is a multifactorial neurodegenerative disease, and the cause of this disease is still unknown. However, several hypotheses try to explain the aetiology of the disease, such as Aβ hypothesis, metal ion hypothesis, calcium homeostasis, cholinergic hypothesis, tau propagation, etc. Scientific literature reports several derivatives that show potential to treat Alzheimer’s disease. Primarily these compounds act on nuclear receptors to activate ADAM10, inhibiting AChE or BuChE, neutralisation of ROS, inhibition of GSK-3, and amyloid-beta aggregation. Moreover, some can easily pass the BBB, which is crucial in targeting neurological disease. Vitamins and their derivatives show promising results in managing Alzheimer’s disease, even several are in clinical trials.

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Abbreviations

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

ADAM10:

A Disintegrin metalloproteinase 10

APL:

Acute promyelocytic leukaemia

ApoE:

Apolipoprotein E

APP:

Amyloid precursor protein

ATP:

Adenosine triphosphate

ATRA:

All-trans RA

Aβ:

Amyloid-beta

BACE1:

Beta-site APP-cleaving enzyme 1

BBB:

Blood-brain barrier

BEXA:

Bexarotene

BFT:

Benfotiamine

BHQ:

Biotin-8-hydroxyquinoline

BuChE:

Butyrylcholinesterase

CAS:

Catalytic anionic site

CNS:

Central nervous system

COVID-19:

Coronavirus disease 2019

COX:

Cyclooxygenase

DBT:

Dibenzoylthiamine

DNA:

Deoxyribonucleic acid

FDA:

Food and Drug Administration

GLUT:

Glucose transporters

GSH:

Glutathione

GSK-3:

Glycogen synthase kinase 3

HBHQ:

8-Hydroxyquinolyl-biotin hydrazine

IL-6:

Interleukin-6

LPS:

Lipopolysaccharides

MAO-B:

Monoamine oxidase B

MAPK:

Mitogen-activated protein kinase

MARRS:

Membrane-associated, rapid response steroid-binding

MEM:

Memantine

NAD:

Nicotinamide adenine dinucleotide

NADP:

Nicotinamide adenine dinucleotide phosphate

NEP:

Neprilysin

NMDA:

N-Methyl-d-aspartate

PAS:

Peripheral anionic site

RA:

Retinoic acid

RAR-α:

Retinoic acid receptor alpha

RNA:

Ribonucleic acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

RXR:

Retinoid X receptor

SVCT1:

Sodium-dependent vitamin C transporter-1

SVCT2:

Sodium-dependent vitamin C transporter-2

ThT:

Thioflavin T

TrkB:

Tyrosine kinase receptor B

VDR:

Vitamin D receptor

VK:

Vitamin K

VK2:

Vitamin K2

VK3:

Vitamin K3

α-T3:

Αlpha-tocotrienol

α-TOC:

Αlpha-tocopherol

α-TQ:

Alpha-tocopherolquinone

γ-T3:

Gamma-tocotrienol

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Authors and Affiliations

  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India

    Tanmaykumar Varma, Pradnya Kamble, Madhavi Kumari, Vineet Diwakar & Prabha Garg

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  1. Tanmaykumar Varma
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  2. Pradnya Kamble
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Correspondence to Prabha Garg .

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  1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Raebareli, Uttar Pradesh, India

    Abha Sharma

  2. Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology BHU, Varanasi, Uttar Pradesh, India

    Gyan Prakash Modi

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Varma, T., Kamble, P., Kumari, M., Diwakar, V., Garg, P. (2023). Vitamin-Based Derivatives for the Management of Alzheimer’s Disease. In: Sharma, A., Modi, G.P. (eds) Natural Product-based Synthetic Drug Molecules in Alzheimer's Disease. Springer, Singapore. https://doi.org/10.1007/978-981-99-6038-5_12

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