1,720,987 research outputs found
The role of prokineticin 2 in oxidative stress and in neuropathological processes
Full text linkThe prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions
Identification and characterization of prokineticin receptor 2 splicing variant and its modulation in an animal model of alzheimer's disease
Full text linkProkineticin 2 is a peptide that is widely distributed in the nervous system and influences a variety of brain functions, such as pain, food intake and circadian rhythms. We previously demonstrated that, in the animal model of Alzheimer’s disease, induced by the intracerebroventricular administration of Aβ1-42, there is a modulation of the prokineticin system in rat hippocampus.
Prokineticin 2 is a able to mediate its signaling through two different G-protein coupled receptors, designated PKR1 and PKR2, belonging to the neuropeptide Y receptor class. These two receptors have different tissue distributions: PKR1 is expressed in diverse peripheral organs with relatively high levels in the small intestines and lung, whereas PKR2 is predominantly expressed in the central nervous system. The PKRs activate multiple intracellular signal-transduction pathways: they are Gαq-coupled receptors and promoting intracellular calcium mobilization but they also couple to Gαi (especially PKR2) and Gαs proteins.
In rat hippocampus we identified a mRNA encoding for a PKR2 splice variant, that lacking the second exon, gives rise to a four-transmembrane protein denominated TM 4-7. Expression of this splicing variant in yeast, allowed us to demonstrate that TM 4-7 dimerizes with PKR2 long form and that this heterodimer binds to G protein subtypes with different specificity respect to PKR2 wild-type. Moreover we evidenced that, following Aβ1-42 intracerebroventricular injection in rat, the PKR2 hippocampal levels slightly increased respect to control animals whereas there was a strong up-regulation of the PKR2 splicing variant, TM 4-7. We showed that the increased levels of TM 4-7 determined a modulation of PKR2 signal transduction hindering STAT3 activation
Chemokines in Alzheimer’s Disease: New Insights Into Prokineticins, Chemokine-Like Proteins
Full text linkAlzheimer’s disease is the most common neurodegenerative disorder characterized by the presence of β-amyloid aggregates deposited as senile plaques and by the presence of neurofibrillary tangles of tau protein. To date, there is a broad consensus on the idea that neuroinflammation is one of the most important component in Alzheimer’s disease pathogenesis. Chemokines and their receptors, beside the well-known role in the immune system, are widely expressed in the nervous system, where they play a significant role in the neuroinflammatory processes. Prokineticins are a new family of chemokine-like molecules involved in numerous physiological and pathological processes including immunity, pain, inflammation, and neuroinflammation. Prokineticin 2 (PROK2) and its receptors PKR1 and PKR2 are widely expressed in the central nervous system in both neuronal and glial cells. In Alzheimer’s disease, PROK2 sustains the neuroinflammatory condition and contributes to neurotoxicity, since its expression is strongly upregulated by amyloid-β peptide and reversed by the PKR antagonist PC1. This review aims to summarize the current knowledge on the neurotoxic and/or neuroprotective function of chemokines in Alzheimer’s disease, focusing on the prokineticin system: it represents a new field of investigation that can stimulate the research of innovative pharmacotherapeutic strategies
The balance of concentration between Prokineticin 2β and Prokineticin 2 modulates the food intake by STAT3 signaling
Full text linkThe secreted bioactive peptide prokineticin 2 (PK2) is a potent adipokine and its central and peripheral administration reduces food intake in rodents. The pk2 gene has two splice variants, PK2 and PK2L (PK2 long form), which is cleaved into an active peptide, PK2β, that preferentially binds prokineticin receptor 1 (PKR1). We investigated the role of PK2β in the regulation of food intake. We demonstrated that intraperitoneal injection of PK2β, in contrast to PK2, did not reduce food intake in mice. Exposure of hypotalamic explants to PK2, but not PK2β, induced phosphorylation of STAT3 and ERK. We also evidenced that in adipocytes from PKR1 knock-out mice, a model of obesity, there were higher PK2β levels than PK2 inducing a decreased activation of STAT3 and ERK. Our results suggest that variations in PK2 and PK2β levels, due to modulation of pk2 gene splicing processes, affect food intake in mice
Potential clinical role of Prokineticin 2 (PK2) in neurodegenerative diseases
No full textThe role of the immune system in neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) has become clear in recent decades, as evidenced by the presence of activated microglia and astrocytes and numerous soluble mediators in the brain and peripheral tissues of affected patients. Among inflammatory mediators, chemokines play a central role in neuroinflammation due to their dual function as chemoattractants for immune cells and as molecular messengers in crosstalk among CNS-resident cells. The chemokine Bv8/Prokineticin 2 (PK2) has recently emerged as an important player in many age-related and chronic diseases that are either neurodegenerative or systemic. In this perspective paper, we briefly discuss the role that PK2 and its cognate receptors play in AD and PD animal models and in human patients. Given the apparent changes in PK2 blood levels in both AD and PD patients, the potential clinical value of PK2 either as a disease biomarker or as a therapeutic target for these disorders is discussed
Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1
No full text: The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 °C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 °C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and-pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1-/- than in PKR2-/- mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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