Prokineticin signaling in heart-brain developmental axis: Therapeutic options for heart and brain injuries

Abstract

Heart and brain development occur simultaneously during the embryogenesis, and both organ development and injuries are interconnected. Early neuronal and cardiac injury share mutual cellular events, such as angiogenesis and plasticity that could either delay disease progression or, in the long run, result in detrimental health effects. For this reason, the common mechanisms provide a new and previously undervalued window of opportunity for intervention.Because angiogenesis, cardiogenesis and neurogenesis are essential for the development and regeneration of the heart and brain, we discuss therein the role of prokineticin as an angiogenic neuropeptide in heart-brain development and injuries. We focus on the role of prokineticin signaling and the effect of drugs targeting prokineticin receptors in neuroprotection and cardioprotection, with a special emphasis on heart failure, neurodegenerative Parkinson's disease and ischemic heart and brain injuries. Indeed, prokineticin triggers common pro-survival signaling pathway in heart and brain.Our review aims at stimulating researchers and clinicians in neurocardiology to focus on the role of prokineticin signaling in the reciprocal interaction between heart and brain. We hope to facilitate the discovery of new treatment strategies, acting in both heart and brain degenerative diseases.

Interplay between Prokineticins and Histone Demethylase KDM6A in a Murine Model of Bortezomib-Induced Neuropathy

“…It was also suggested that the overexpression of PK2 and PKR2 on activated astrocytes can act as an astrocytic-autocrine-growth factor [ 13 ]. In support of PK2 feed forward loop, Nebigil’s group [ 41 ] demonstrated that PKR1 signaling in cardiomyocyte upregulates PK2, which acts as a paracrine factor for triggering the proliferation/differentiation of epicardial-derived progenitor cells (EDPC) [ 41 ]. As a consequence, and in line with previous studies [ 11 ], the repeated administration of the PKRs antagonist PC1 was able to counteract allodynia signs, causing a significant elevation of mechanical thresholds of BTZ-treated mice up to control values at the 28th day.…”

Prokineticin-Receptor Network: Mechanisms of Regulation

“…Prokineticin receptors (PKRs) are seven-transmembrane G protein-coupled receptors (GPCRs), designated PKR1 and PKR2. PKRs can signal through the G αs and G αi proteins, modulating adenylate cyclase, as well as through the G q proteins, promoting intracellular Ca 2+ increase and protein kinase C activation, via the phospholipase C (PLC) pathway [5].…”

Potential Clinical Role of Prokineticin 2 (PK2) in Neurodegenerative Diseases

“…Among chemokines, Bv8/Prokineticin 2 (PK2) has recently emerged as an important player in many age-related and chronic neurodegenerative or systemic diseases [ 12 , 13 ]. PK2 interacts with two G protein-coupled receptors (PKR 1 and PKR 2 ) and is involved in multiple biological pathways at a multisystemic level.…”

“…Instead, targeting the PK2 pathway may pave the way for novel therapeutic strategies. Indeed, PK2 activates a defensive cellular response that counteracts oxidative stress, metabolic disturbances, proteinopathy, and glutamate toxicity [ 14 ] and also protects against traumatic brain injury and cerebral ischemia [ 13 ], which are two major factors in the development and progression of PD [ 28 , 29 ].…”