Participation of the kinin-kalicrein system and kinin receptors in the development of the Alzheimer's disease

• Grant number: 07/04800-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2008
• End date: April 30, 2010
• Field of knowledge: Biological Sciences - Pharmacology - Neuropsychopharmacology
• Principal Investigator: Hudson de Sousa Buck
• Grantee: Hudson de Sousa Buck
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

Kinin effects are mediated by the activation of G protein coupled B1 and B2 receptors. The B2 receptor is expressed in most tissues while B1 generally is not expressed in physiological conditions. The induction and increase in the expression of B1 receptor may occur by tissue injure, bacterial endotoxins, some cytocins, growth factors and during chronic neurodiseases. Recently we described an evident neurodegeneration in cortical and hippocampal areas associated to amyloid-beta deposits, increase of bradykinin in the cerebrospinal fluid and increase of B1 and B2 receptors binding sites in areas related to cognitive process after the chronic infusion of the amyloid-beta human peptide. In addition, the activation of kinin receptors may stimulate the release of amyloid precursor protein (APP). These facts reinforce the involvement of the kinin-kalicrein system in the pathology of Alzheimer's disease. However, if the activation of the kinin-kalicrein system is the cause or consequence of an association to the inflammatory process, is still unclear. By this way, applying active and inhibitory avoidance tests to evaluate cognitive functions, chronic infusion of amyloid-beta peptide and/or bradykinin in the lateral ventricles, "in vitro" autoradiography for B1 and B2 receptors, real-time PCR and immunohistochemistry to B1 or B2 receptors knock-out mice and transgenic mice over expressing the human APP, we intend to ascertain the participation of kinin-kalicrein system and its receptors in the pathogenesis of the Alzheimer's disease. This investigation can offer new sights for therapeutically approaches of chronic neurodiseases. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CAETANO, A. L.; DONG-CRESTE, K. E.; AMARAL, F. A.; MONTEIRO-SILVA, K. C.; PESQUERO, J. B.; ARAUJO, M. S.; MONTOR, W. R.; VIE, T. A.; BUCK, H. S.. Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease. Neuropeptides, v. 53, p. 51-62, OCT 2015. (09/08049-3, 07/04800-0, 13/13656-1)

AMARAL‚ F.A.; LEMOS‚ M.T.R.; DONG‚ K.E.; BITTENCOURT‚ M.F.Q.P.; CAETANO‚ A.L.; PESQUERO‚ J.B.; VIEL‚ T.A.; BUCK‚ H.S.. Participation of kinin receptors on memory impairment after chronic infusion of human amyloid-[beta] 1-40 peptide in mice. Neuropeptides, v. 44, n. 2, p. 93-97, 2010. (07/04800-0)

CAETANO, ARIADINY LIMA; VIEL, TANIA ARAUJO; QUEIROZ PRADO BITTENCOURT, MARIA FERNANDA; ARAUJO, MARIANA SILVA; DE ANGELIS, KATIA; BUCK, HUDSON SOUSA. Change in central kinin B2 receptor density after exercise training in rats. AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, v. 158, n. 1-2, p. 71-78, DEC 8 2010. (07/04800-0)

LEMOS‚ M.T.R.; AMARAL‚ F.A.; DONG‚ K.E.; BITTENCOURT‚ M.F.Q.P.; CAETANO‚ A.L.; PESQUERO‚ J.B.; VIEL‚ T.A.; BUCK‚ H.S.. Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice. Neuropeptides, v. 44, n. 2, p. 163-168, 2010. (07/04800-0)