Kallikrein-Kinin System Mediated Inflammation in Alzheimers Disease In Vivo

Abstract

The Kallikrein-Kinin System (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer's disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (Aβ) peptide in rats, which was accompanied by memory disruption and neuronal loss. Mice lacking B1 or B2 receptors presented reduced cognitive deficits related to the learning process, after acute intracerebroventricular (i.c.v). administration of Aβ. Nevertheless, our group showed an early disruption of cognitive function by i.c.v. chronic infusion of Aβ after a learned task, in the knock-out B2 mice. This suggests a neuroprotective role for B2 receptors. In knock-out B1 mice the memory disruption was absent, implying the participation of this receptor in neurodegenerative processes. The acute or chronic infusion of Aβ can lead to different responses of the brain tissue. In this way, the proper involvement of KKS on neuroinflammation in AD probably depends on the amount of Aβ injected. Though, BK applied to neurons can exert inflammatory effects, whereas in glial cells, BK can have a potential protective role for neurons, by inhibiting proinflammatory cytokines. This review discusses this duality concerning the KKS and neuroinflammation in AD in vivo.

Human Neuropsin Gene in Depression

“…The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins (Viel & Buck 2011). Increased expression of hNP in people with depression, as a defense reaction of the organism against disease recurrence, is only a hypothesis which can be verified in subsequent studies.…”

Involvement of Extracellular Signal-Regulated Kinase 5 in Kinin B1 Receptor Upregulation in Isolated Human Umbilical Veins

“…The activation of kinin B 1 receptors has also been associated to inflammatory and immunogenic responses in the peripheral and central nervous system. In this sense, Viel and Buck (2011) demonstrated the participation of kinin B 1 receptor in neurodegenerative processes, suggesting a link between this receptor and the neuroinflammation in Alzheimer disease. Moreover, da Costa et al (2014) have shown evidence that supports the concept that kinin receptors, especially kinin B 1 receptor, are promising targets for cancer therapy, since many tumor cells express aberrantly high levels of these receptors.…”

Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis

“…Similar to BD, one of the main pathology in AD is the neuroinflammatory process. In AD, both B1BKR and B2BKR are expressed in the affected brain regions of patients with early onset of the disease (Viel and Buck, 2011). It has been suggested that the B2BKR acts as a neuroprotective receptor, while B1BKR functions as a pro-inflammatory one.…”

“…It has been suggested that the B2BKR acts as a neuroprotective receptor, while B1BKR functions as a pro-inflammatory one. Like BD, Alzheimer's disease is characterized by the high levels of IL-1β, TNF-α and NF-κB upregulating B1BKR expression levels (Passos et al, 2004;Viel and Buck, 2011). When upregulated in its expression and activity, the receptor increases in pro-inflammatory cytokine production and release.…”