Review
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World J Biol Chem. May 26, 2014; 5(2): 130-140
Published online May 26, 2014. doi: 10.4331/wjbc.v5.i2.130
What have we learned about the kallikrein-kinin and renin-angiotensin systems in neurological disorders?
Maria da Graça Naffah-Mazzacoratti, Telma Luciana Furtado Gouveia, Priscila Santos Rodrigues Simões, Sandra Regina Perosa
Maria da Graça Naffah-Mazzacoratti, Telma Luciana Furtado Gouveia, Priscila Santos Rodrigues Simões, Sandra Regina Perosa, Department de Bioquímica and Departamento de Neurologia/Neurocirurgia, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 4039032, Brazil
Author contributions: Gouveia TLF worked on renin-angiotensin systems in epilepsy; Simões PSR worked on kallikrein and other enzymes related to this system; and Perosa SR worked with kinins and their receptors in the CNS; Naffah-Mazzacoratti MG guided all the work, wrote and organized the manuscript.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); and Instituto Nacional de Neurociência Translacional (INNT), Programa de Núcleos de Excelência (PRONEX) (Brazil)
Correspondence to: Maria da Graça Naffah-Mazzacoratti, PhD, Departamento de Bioquímica, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, segundo andar, São Paulo, SP 4039032, Brasil. naffahmazzacoratti@gmail.com
Telephone: +55-11-55764848-1356 Fax: +55-11-55764848-2838
Received: November 15, 2013
Revised: February 10, 2014
Accepted: March 17, 2014
Published online: May 26, 2014
Processing time: 209 Days and 9.7 Hours
Abstract

The kallikrein-kinin system (KKS) is an intricate endogenous pathway involved in several physiological and pathological cascades in the brain. Due to the pathological effects of kinins in blood vessels and tissues, their formation and degradation are tightly controlled. Their components have been related to several central nervous system diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, epilepsy and others. Bradykinin and its receptors (B1R and B2R) may have a role in the pathophysiology of certain central nervous system diseases. It has been suggested that kinin B1R is up-regulated in pathological conditions and has a neurodegenerative pattern, while kinin B2R is constitutive and can act as a neuroprotective factor in many neurological conditions. The renin angiotensin system (RAS) is an important blood pressure regulator and controls both sodium and water intake. AngII is a potent vasoconstrictor molecule and angiotensin converting enzyme is the major enzyme responsible for its release. AngII acts mainly on the AT1 receptor, with involvement in several systemic and neurological disorders. Brain RAS has been associated with physiological pathways, but is also associated with brain disorders. This review describes topics relating to the involvement of both systems in several forms of brain dysfunction and indicates components of the KKS and RAS that have been used as targets in several pharmacological approaches.

Keywords: Kallikrein-kinin system; Renin-angiotensin system; Neurological disorders; Alzheimer’s disease; Epilepsy; Parkinson’s disease

Core tip: This review is a description of the involvement of the kallikrein-kinin and renin-angiotensin systems in neurological disorders. We describe all components of both systems, relating them to several brain diseases such as Alzheimer’s disease, Parkinson’s disease, epilepsy, multiple sclerosis, blood brain barrier disruption, stroke and inflammation, including the involvement of each molecule, their receptor and specific enzymes in individual pathologies. We also show that brain homeostasis depends on a dynamic balance between the kallikrein-kinin and renin-angiotensin systems.