Tackling Neuroinflammation in Cognitive Disorders with Single-Targeted and Multi-Targeted Histamine H₃ Receptor Modulators

Author(s)

Lopes, Flavia Barrio ; Fernandes, Joao Paulo S. ; Uliassi, Elisa

• Document type: Journal article
• Source: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 24, n. 28, p. 10-pg., 2024-08-23.

Abstract

Neuroinflammation is a process involved in a variety of central nervous system (CNS) diseases and is being increasingly recognized as a key mediator of cognitive impairments. Neuroinflammatory responses including glial activation, increased production of proinflammatory cytokines, and aberrant neuronal signaling, contribute to cognitive dysfunctions. Histamine is a key peripheral inflammatory mediator, but plays an important role in neuroinflammatory processes as well. The unique localization of histamine H-3 receptor (H3R) in the CNS along with the modulation of the release of other neurotransmitters via its action on heteroreceptors on non-histaminergic neurons have led to the development of several H3R ligands for various brain diseases. H3R antagonists/inverse agonists have revealed potential to treat diverse neuroinflammatory CNS disorders, including neurodegenerative diseases, attention-deficit hyperactivity syndrome and schizophrenia. In this mini review, we provide a brief overview on the crucial involvement of the histaminergic transmission in the neuroinflammatory processes underlying these cognitive disorders, with a special focus on H3R involvement. The anti-neuroinflammatory potential of single-targeted and multi-targeted H3R antagonists/inverse agonists for the treatment of these conditions is discussed here. (AU)

• FAPESP's process: 23/03485-7 - Dual H3R/QC inhibitors as alternatives for the treatment of neurodegenerative diseases
• Grantee: Flávia Barrio Lopes
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/24028-8 - Substituted aryl-alkylamide-piperazines as multitarget ligands: synthesis and assessment of the activity on relevant targets for the treatment of CNS disorders
• Grantee: João Paulo dos Santos Fernandes
• Support Opportunities: Regular Research Grants