TY - JOUR
T1 - Implication of the Kallikrein-Kinin system in neurological disorders
T2 - Quest for potential biomarkers and mechanisms
AU - Nokkari, Amaly
AU - Abou-El-Hassan, Hadi
AU - Mechref, Yehia
AU - Mondello, Stefania
AU - Kindy, Mark S.
AU - Jaffa, Ayad A.
AU - Kobeissy, Firas
N1 - Funding Information:
This work is supported by a grant from the Lebanese National Council for Scientific Research (CNRS) and from the Medical Practice Plan, Faculty of Medicine, AUB grant support: “Dual Neurotherapeutic Effects of Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) with Neonatal Neural Stem Cell transplantation Post-Traumatic Brain Injury” (FK), and from the National Heart, Lung and Blood Institute, National Institutes of Health (NIH) grant R01-HL077192 (AAJ).
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2018/6/1
Y1 - 2018/6/1
N2 - Neurological disorders represent major health concerns in terms of comorbidity and mortality worldwide. Despite a tremendous increase in our understanding of the pathophysiological processes involved in disease progression and prevention, the accumulated knowledge so far resulted in relatively moderate translational benefits in terms of therapeutic interventions and enhanced clinical outcomes. Aiming at specific neural molecular pathways, different strategies have been geared to target the development and progression of such disorders. The kallikrein-kinin system (KKS) is among the most delineated candidate systems due to its ubiquitous roles mediating several of the pathophysiological features of these neurological disorders as well as being implicated in regulating various brain functions. Several experimental KKS models revealed that the inhibition or stimulation of the two receptors of the KKS system (B1R and B2R) can exhibit neuroprotective and/or adverse pathological outcomes. This updated review provides background details of the KKS components and their functions in different neurological disorders including temporal lobe epilepsy, traumatic brain injury, stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis and glioma. Finally, this work will highlight the putative roles of the KKS components as potential neurotherapeutic targets and provide future perspectives on the possibility of translating these findings into potential clinical biomarkers in neurological disease.
AB - Neurological disorders represent major health concerns in terms of comorbidity and mortality worldwide. Despite a tremendous increase in our understanding of the pathophysiological processes involved in disease progression and prevention, the accumulated knowledge so far resulted in relatively moderate translational benefits in terms of therapeutic interventions and enhanced clinical outcomes. Aiming at specific neural molecular pathways, different strategies have been geared to target the development and progression of such disorders. The kallikrein-kinin system (KKS) is among the most delineated candidate systems due to its ubiquitous roles mediating several of the pathophysiological features of these neurological disorders as well as being implicated in regulating various brain functions. Several experimental KKS models revealed that the inhibition or stimulation of the two receptors of the KKS system (B1R and B2R) can exhibit neuroprotective and/or adverse pathological outcomes. This updated review provides background details of the KKS components and their functions in different neurological disorders including temporal lobe epilepsy, traumatic brain injury, stroke, spinal cord injury, Alzheimer's disease, multiple sclerosis and glioma. Finally, this work will highlight the putative roles of the KKS components as potential neurotherapeutic targets and provide future perspectives on the possibility of translating these findings into potential clinical biomarkers in neurological disease.
KW - Biomarkers
KW - Bradykinin
KW - Brain injury
KW - Kallikrein-Kinin system
KW - Kinin
KW - Neurological disorders
UR - http://www.scopus.com/inward/record.url?scp=85040911893&partnerID=8YFLogxK
U2 - 10.1016/j.pneurobio.2018.01.003
DO - 10.1016/j.pneurobio.2018.01.003
M3 - Review article
C2 - 29355711
AN - SCOPUS:85040911893
VL - 165-167
SP - 26
EP - 50
JO - Progress in Neurobiology
JF - Progress in Neurobiology
SN - 0301-0082
ER -