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Serotonin Receptors as a Potential Target in the Treatment of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most common cause of dementia worldwide that has an increasing impact on aging societies. Besides its critical role in the control of various physiological functions and behavior, brain serotonin (5-HT) system is involved in the regulation of migration, proliferation, differentiation, maturation, and programmed death of neurons. At the same time, a growing body of evidence indicates the involvement of 5-HT neurotransmission in the formation of insoluble aggregates of β-amyloid and tau protein, the main histopathological signs of AD. The review describes the role of various 5-HT receptors and intracellular signaling cascades induced by them in the pathological processes leading to the development of AD, first of all, in protein aggregation. Changes in the functioning of certain types of 5-HT receptors or associated intracellular signaling mediators prevent accumulation of β-amyloid plaques and tau protein neurofibrillary tangles. Based on the experimental data, it can be suggested that the use of 5-HT receptors as new drug targets will not only improve cognitive performance in AD, but will be also important in treating the causes of AD-related dementia.

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Abbreviations

Aβ:

β-amyloid

AD:

Alzheimer’s disease

5-HT:

serotonin

APP:

amyloid precursor protein

CaM:

calmodulin

CDK5:

cyclin-dependent kinase 5

ERK1/2:

extracellular signal-regulated kinases 1/2

Fyn:

proto-oncogene tyrosine protein kinase Fyn

GIP:

GPCR-interacting protein

GPCR:

G protein-coupled receptor

GRK5:

G protein-coupled receptor kinase 5

CRMR2:

collapsin response mediator protein 2

GSK-3β:

glycogen synthase kinase-3 beta

LTP:

long-term potentiation

PKA:

protein kinase A

PSD-95:

postsynaptic density protein 95

PTEN:

phosphatase and tensin homolog

sAPPα:

soluble amyloid precursor protein

SAP97:

synapse-associated protein 97

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Funding

The work was supported by the Russian Science Foundation (project no. 22-15-00011).

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 630090, Novosibirsk, Russia

    Dmitrii V. Eremin, Elena M. Kondaurova, Aleksander Ya. Rodnyy, Camilla A. Molobekova & Vladimir S. Naumenko

  2. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 119991, Moscow, Russia

    Dmitrii A. Kudlay

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  1. Dmitrii V. Eremin
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D.V.E. and E.M.K. wrote and edited the manuscript; A.Ya.R. created the figures and provided description of intracellular mechanisms; C.A.M. wrote the manuscript; D.A.K. edited the manuscript; V.S.N. supervised the study, edited the manuscript, and provided funding.

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Eremin, D.V., Kondaurova, E.M., Rodnyy, A.Y. et al. Serotonin Receptors as a Potential Target in the Treatment of Alzheimer’s Disease. Biochemistry Moscow 88, 2023–2042 (2023). https://doi.org/10.1134/S0006297923120064

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