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

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Dmitrii V. Eremin^1,a*, Elena M. Kondaurova¹, Aleksander Ya. Rodnyy¹, Camilla A. Molobekova¹, Dmitrii A. Kudlay², and Vladimir S. Naumenko¹

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

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

^* To whom correspondence should be addressed.

Received July 3, 2023; Revised September 26, 2023; Accepted September 29, 2023

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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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KEY WORDS: Alzheimer’s disease, brain serotonin system, 5-HT receptors, β-amyloid, tau protein, protein aggregation

DOI: 10.1134/S0006297923120064

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