Evaluation of the Kallikrein-Kinin System at neurogenesis, proliferation and differentiation level of neuronal precursors from Amyotrophic Lateral Sclerosis patients.

• Grant number: 13/25338-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): April 01, 2014
• Effective date (End): April 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Laura Sardá Arroyo
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 15/12935-0 - Kallikrein-kinin system evaluation in neurogenesis, proliferation and differentiation of neural progenitor cells from amyotrophic lateral sclerosis patients to mature motor neurons, BE.EP.DR

Abstract

Kinins are biological active peptides which get activated through proteolytic cleavage by kallikrein enzymes. Kinins are known for their involvement in the inflammation process and in cardiac regulation. Recent studies broaden the spectrum of physiological functions carried out by kinins. In vivo experiments showed that bradykinin (BK), an active kinin, increases neurogenesis events in different cellular types (embrionary telencephalon stem cells and murin P19 cells) through bradykinin 2 receptor (B2BKR) activation. On the other hand B2BKR inhibition by HOE-140 promotes gliogenesis. Preliminary studies done by our group showed an improvement in behavioral tests and immunohistochemical assays in a 6-OHDA rat model treated with BK. It has been shown, that modulation of B2BKR activity is involved in cellular death in neurodegenerative diseases. So far the involvement of neither the kallikrein-kinin system (KKS) nor of BK has ever been studied at Amyotrophic Lateral Sclerosis (ALS) disease. Therefore we propose the study of the KKS in neurogenesis, proliferation and differentiation of induced pluripotente stem cells (iPSC), which will be generated by reprogrammed fibroblasts from ALS patients. In this way we will determine eventual alterations in KKS. The iPSC will be used as a tool for modeling ALS disease and as a neurogenesis model.

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)

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)