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Link to original content: http://pubmed.ncbi.nlm.nih.gov/35725396/
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Review
. 2022 Jun 20;28(1):70.
doi: 10.1186/s10020-022-00497-2.

Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases

Alejandro Quintero-Villegas  1   2 , Sergio Iván Valdés-Ferrer  3   4   5
Affiliations
Review

Central nervous system effects of 5-HT7 receptors: a potential target for neurodegenerative diseases

Alejandro Quintero-Villegas et al. Mol Med. .

Abstract

5-HT7 receptors (5-HT7R) are the most recently identified among the family of serotonin receptors. Their role in health and disease, particularly as mediators of, and druggable targets for, neurodegenerative diseases, is incompletely understood. Unlike other serotonin receptors, for which abundant preclinical and clinical data evaluating their effect on neurodegenerative conditions exist, the available information on the role of the 5-HT7R receptor is limited. In this review, we describe the signaling pathways and cellular mechanisms implicated in the activation of the 5-HT7R; also, we analyze different mechanisms of neurodegeneration and the potential therapeutic implications of pharmacological interventions for 5-HT7R signaling.

Keywords: 5-HT7; Alzheimer disease; Dementia; Neurodegeneration; Neuroprotection; Parkinson disease.

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Conflict of interest statement

The authors declare no conflicts of interest while making this article.

Figures

Fig. 1
Fig. 1
5-HT7 and 5-HT1A receptor signaling pathways and oligo/heterodimer formation. 5-HT7 receptor monomers (in yellow) can form homodimers or homoligomers, with the same signaling pathways and cellular effects. 5-HT7 can also form heterodimers or heteroligomers with 5-HT1A (in teal), resulting in the inhibition of the 5-HT1A signaling pathway, with no net effect downstream of 5-HT7. When activated, 5-HT7 activates Gas (canonical pathway) with a subsequent signaling cascade that results in the activation of ERK (also known as MAPK) and Akt; in contrast, the activation of Ga12 activates mTOR and different Rho family small GTPases. As illustrated, the phosphorylation of Trkb is mediated by both G proteins. AC adenylate cyclase, cAMP cyclic adenosine monophosphate, Cdc42 cell division control protein 42 homolog, ERK extracellular signal-regulated kinases, MAPK mitogen-activated protein kinases, mTOR mammalian target of rapamycin, Trkb Tropomyosin receptor kinase B
Fig. 2
Fig. 2
Cellular and molecular effects of 5-HT7 receptors. Molecular effects of 5-HT7 activation. A When activated, 5-HT7 receptors modulate ion transmission through enhancing LTP and LTD (1); these receptors also increase the number of neurotrophins (especially BDNF) and the affinity of its receptor Trkb (2); through ERK and Akt, 5-HT7 decreases neuronal damage mediated by ROS (3); and reduces the excitotoxicity burden mediated by glutamate-NMDA-calcium. Cellular effects of 5-HT7 activation. B When stimulated by serotonin, 5-HT7 enhances dendritic sprouting and synaptogenesis, while regulating (often towards suppression) immune cells. LTD long-term depression, LTP long-term potentiation, NMDA (N-methyl-d-aspartate receptor, ROS reactive oxygen species, Trkb tropomyosin receptor kinase B
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