Abstract
Prokineticins are a new class of chemokine-like peptides involved in a wide range of biological and pathological activities. In particular, prokineticin 2 (PK2), prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2) play a central role in modulating neuroinflammatory processes. PK2 and PKRs, which are physiologically expressed at very low levels, are strongly upregulated during inflammation and regulate neuronal-glial interaction. PKR2 is mainly overexpressed in neurons, whereas PKR1 and PK2 are mainly overexpressed in astrocytes. Once PK2 is released in inflamed tissue, it is involved in both innate and adaptive responses: it triggers macrophage recruitment, production of pro-inflammatory cytokines, and reduction of anti-inflammatory cytokines. Moreover, it modulates the function of T cells through the activation of PKR1 and directs them towards a pro-inflammatory Th1 phenotype. Since the prokineticin system appears to be upregulated following a series of pathological insults leading to neuroinflammation, we will focus here on the involvement of PK2 and PKRs in those pathologies that have a strong underlying inflammatory component, such as: inflammatory and neuropathic pain, Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, stroke, obesity, diabetes, and gastrointestinal inflammation.
Highlights
prokineticin 2 (PK2) overexpression of pro- and and anti-inflammatory anti-inflammatory cytokines the periphery periphery and and spinal spinal cord, cord, and and reducing reducing procytokines in in both both the spinal glial glial activation activation [35,36]. These results indicate that the the prokineticin prokineticin system system represents represents aa new new potential potential theratheraThese results indicate that peutic target to combat peripheral neuropathy
Neuroinflammation is defined as an inflammatory response within the brain or the spinal cord associated with activation of the glia with significant production of cytokines and chemokines, infiltration of peripheral immune cells, edema, increased permeability and disruption of the blood–brain barrier
Neuroinflammation, which is seen in obesity, diabetes, Parkinson’s and Alzheimer’s, causes several overlapping neurodegenerative mechanisms, including oxidative stress, mitochondrial dysfunction, and inflammation [90,91]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Prokineticin receptors are expressed in many conditions such as: inflammatory and neuropathic pain, Alzheimer’s disease, Parkinson’s tissues and are able to couple different G proteins inducing an extreme variability of redisease, multiple sclerosis, obesity, diabetes and gastrointestinal inflammation. For this stroke, reason, dysregulation in the prokineticin system can lead to inflammatory and neuroinflammatory conditions, as reported in several studies. Schwann cells and injury (SNI) and chronic constriction injury (CCI)], damage to the nerve results in tactile infiltrating macrophages This overexpression spreads towards the DRG and allodynia andspinal thermal hyperalgesia, with upregulation of the PK2 and PKR2 receptors in cord at an interval of 10 days after injury.
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