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Targeting the gastrin-releasing peptide receptor pathway to treat cognitive dysfunction associated with Alzheimer's Disease

O receptor do peptídeo liberador de gastrina como novo alvo terapêutico para o tratamento da disfunção cognitiva associada à Doença de Alzheimer

Abstract

Increasing evidence indicates that bombesin (BB)-like peptides (BLPs), such as the gastrin-releasing peptide (GRP) and its receptor (GRPR), might play a role in neurological and psychiatric disorders. The present study reviews findings from animal and human studies suggesting that the GRPR should be considered a target for the treatment of cognitive dysfunction in patients with Alzheimer's disease (AD). Abnormalities in GRPR-triggered signaling have been described in both fibroblasts from patients with AD, and in transgenic mouse models of AD. Pharmacological and genetic preclinical studies have indicated that BLPs and the GRPR are importantly involved in regulating cognitive function. Moreover, drugs acting at the GRPR have been shown to enhance memory and ameliorate cognitive dysfunction in experimental models of amnesia associated with AD. Taken together, these findings support the view that the GRPR is a novel therapeutic target for the treatment of memory deficits associated with AD.

Key words:
bombesin-like peptides; gastrin-releasing peptide; gastrin-releasing peptide receptor; cognitive enhancers; memory disorders; Alzheimer disease.

Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br