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Potential drugs for the treatment of Alzheimer’s disease

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Abstract

It is well known that amyloid precursor protein (APP), the enzyme β-secretase 1 (BACE1), cyclooxygenase 2 (COX-2), nicastrin (NCT), and hyperphosphorylated tau protein (p-tau) are closely related to the development of Alzheimer’s disease (AD). In addition, recent evidence shows that neuroinflammation also contributes to the pathogenesis of AD. Although the mechanism is not clearly known, such inflammation could alter the activity of the aforementioned molecules. Therefore, the use of anti-inflammatory agents could slow the progression of the disease. Nimesulide, resveratrol, and citalopram are three anti-inflammatory agents that could contribute to a decrease in neuroinflammation and consequently to a decrease in the overexpression of APP, BACE1, COX-2, NCT, and p-Tau, as they possess anti-inflammatory effects that could regulate the expression of APP, BACE1, COX-2, NCT, and p-Tau of potent pro-inflammatory markers indirectly involved in the expression of APP, BACE1, NCT, COX-2, and p-Tau; therefore, their use could be beneficial as preventive treatment as well as in the early stages of AD.

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Data availability statement

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Abbreviations

3,5,4′-Trihydroxy-trans-stilbene:

Resveratrol

AD:

Alzheimer’s disease

AICD:

APP intracellular domain

APH-1A/APH-1B:

Anterior pharyngeal deficiency 1A or 1B

APP:

Amyloid precursor protein

BACE1:

Enzyme β-secretase 1

COX-2:

Cyclooxygenase 2

CTFα:

C-terminal fragment alpha

CTFβ:

C-terminal beta

FDA:

Food and drug administration

GSK-3β:

Glycogen synthase kinase-3 beta

IFN-γ:

Interferon gamma

IL:

Interleukins

iNOS:

Inducible nitric oxide synthase

MMP9:

Matrix metallopeptidase 9

NADPH:

Nicotinamide adenine dinucleotide phosphate

NCT:

Nicastrin

NF-κβ:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NO:

Nitric oxide

NOX:

NADPH oxidase

NSAIDs:

Non-steroidal anti-inflammatory drugs

p-Tau:

Hyperphosphorylated Tau protein

PEN-2:

Presenilin enhancer 2

PGs:

Prostaglandins

PS1/PS2:

Presenilins

ROS:

Reactive oxygen species

sAPPα:

Soluble APPα peptide

sAPPβ:

Soluble APPβ

SSRIs:

Selective serotonin reuptake inhibitors

TGF-β:

Transforming growth factor beta

TLR4:

Toll-like receptors

TNF-α:

Tumour necrosis factor-alpha

WHO:

World health organization

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Authors and Affiliations

  1. Facultad de Química, Universidad Veracruzana, Xalapa, Veracruz, México

    Tania Guadalupe Montero-Cosme & Luz Irene Pascual-Mathey

  2. Instituto de Investigaciones Cerebrales, Universidad Veracruzana, Xalapa, Veracruz, México

    María Elena Hernández-Aguilar, Deissy Herrera-Covarrubias, Fausto Rojas-Durán & Gonzalo Emiliano Aranda-Abreu

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TGM-C: the main author of the manuscript. LIP-M, MEH-A, DH-C, FR-D: review and approval of the manuscript. GEA-A: review, approval, manuscript editor and corresponding author.

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Montero-Cosme, T.G., Pascual-Mathey, L.I., Hernández-Aguilar, M.E. et al. Potential drugs for the treatment of Alzheimer’s disease. Pharmacol. Rep 75, 544–559 (2023). https://doi.org/10.1007/s43440-023-00481-5

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