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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 24, n. 28, p. 10-pg., 2024-08-23.

Resumo

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)

• Processo FAPESP: 23/03485-7 - Inibidores duais H3R/QC como alternativas para o tratamento de doenças neurodegenerativas
• Beneficiário: Flávia Barrio Lopes
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/24028-8 - Aril-alquilamido-piperazinas substituídas como ligantes multialvo: síntese e avaliação da atividade em alvos relevantes para o tratamento de desordens do SNC
• Beneficiário: João Paulo dos Santos Fernandes
• Modalidade de apoio: Auxílio à Pesquisa - Regular