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

Biochemistry (Mosc). 2023 Dec;88(12):2023-2042. doi: 10.1134/S0006297923120064.

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.

Keywords: 5-HT receptors; Alzheimer’s disease; brain serotonin system; protein aggregation; tau protein; β-amyloid.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Humans
  • Receptors, Serotonin / therapeutic use
  • Serotonin
  • tau Proteins / metabolism

Substances

  • tau Proteins
  • Serotonin
  • Amyloid beta-Peptides
  • Receptors, Serotonin