Role of kinins receptor B2 in therapy of Parkinson's Disease in animal model.

• Grant number: 12/20685-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2013
• End date: May 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Héllio Danny Nóbrega de Souza
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 06/61285-9 - Molecular basis of differentiation of stem and neural progenitor cells, AP.TEM

Abstract

Parkinson´s disease (PD) , a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons in the substantia nigra and its projections into the striatum causing various motor deficits. Nowadays, treatment mostly relies on L-DOPA administration; however, effects produced by this drug are limited and cause diverse side effects. Treatment of PD is initiated at progressed stages of PD, since symptoms only become evident after a loss of at least 50 % of dopaminergic neurons in the substantia nigra accompanied by a drastic reduction of dopamine content in the striatum. The slow and progressive death of dopaminergic neurons let to suggest therapeutic strategies aiming at protection of the remaining ones against apoptosis and stimulation of neurogenesis for replacement of lost neurons. In view of that, the exploration of neuroprotective, self-renewal of stem cells inducing and neuroregenerative properties of bradykinin may help to substitute lost dopaminergic neurons in addition to enhance the survival of reminiscent neurons. Actions of bradykinin and its kinin-B2 receptor are implicated in a many physiological contexts, beside its crucial importance in cardiovascular homeostasis and inflammation. Recent results of our group have already shown the participation of bradykinin in neuroregeneration in a rat model of PD induced 6-OH-dopamine injection. Bradykinin injection following establishment of PD symptom's resulted in improvements in the lesioned areas as studied by tyrosine hydroxylase immunostaining and motor functions. Based on these results we now propose to study underlying mechanism of bradykinin actions, including mobilization, attraction and differentiation of neural stem cells, modulation of immune responses as well as establishing effects of bradykinin analogues and inhibitors of bradykinin degradation.

Scientific publications

(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)

FERRAZOLI, ENEAS G.; DE SOUZA, HELLIO D. N.; NASCIMENTO, ISIS C.; OLIVEIRA-GIACOMELLI, AGATHA; SCHWINDT, TELMA T.; BRITTO, LUIZ R.; ULRICHT, HENNING. Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease. CELL TRANSPLANTATION, v. 26, n. 4, SI, p. 669-677, 2017. (15/18730-0, 11/09852-4, 12/20685-5, 12/50880-4)

OLIVEIRA-GIACOMELLI, AGATHA; NAALDIJK, YAHAIRA; SARDA-ARROYO, LAURA; GONCALVES, MARIA C. B.; CORREA-VELLOSO, JULIANA; PILLAT, MICHELI M.; DE SOUZA, HELLIO D. N.; ULRICH, HENNING. Purinergic Receptors in Neurological Diseases With Motor Symptoms: Targets for Therapy. FRONTIERS IN PHARMACOLOGY, v. 9, APR 10 2018. (12/20685-5, 12/50880-4, 15/14343-2, 13/25338-4)

FERRAZOLI, ENEAS G.; DE SOUZA, HELLIO D. N.; NASCIMENTO, ISIS C.; OLIVEIRA-GIACOMELLI, AGATHA; SCHWINDT, TELMA T.; BRITTO, LUIZ R.; ULRICHT, HENNING. Brilliant Blue G, But Not Fenofibrate, Treatment Reverts Hemiparkinsonian Behavior and Restores Dopamine Levels in an Animal Model of Parkinson's Disease. CELL TRANSPLANTATION, v. 26, n. 4, p. 9-pg., 2017-01-01. (12/20685-5, 15/18730-0, 11/09852-4, 12/50880-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Héllio Danny Nóbrega de. Targeting Kinin-B2 receptors for the treatment of dopaminergic neurodegeneration in an animal mode. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.