Targeting

the gastrin-releasing peptide receptor pathway to treat cognitive dysfunction associated with Alzheimer’s Disease Rafael Roesler1,2, Tatiana Luft1,3, Gilberto Schwartsmann2,4 Abstract – Increasing evidence indicates that bombesin (BB)-like peptides (BLPs), such as the gastrin-releas-ing peptide (GRP) and its receptor (GRPR), might play a role in neurological and psychiatric disorders. The present study reviews fi ndings 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 fi broblasts 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 fi ndings support the view that the GRPR is a novel therapeutic target for the treatment of memory defi cits associated with AD. Key words: bombesin-like peptides, gastrin-releasing peptide, gastrin-releasing peptide receptor, cognitive en