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Systemic Administration of a Brain Permeable Cdk5 Inhibitor Alters Neurobehavior
Cyclin-dependent kinase 5 (Cdk5) is a crucial regulator of neuronal signal transduction. Cdk5 activity is implicated in various neuropsychiatric and neurodegenerative conditions such as stress, anxiety, depression, addiction, Alzheimer’s disease, and Parkinson’s disease. While constitutive Cdk5 knockout is perinatally lethal, conditional knockout mice display resilience to stress-induction, enhanced cognition, neuroprotection from stroke and head trauma, and ameliorated neurodegeneration. Thus, Cdk5 represents a prime target for treatment in a spectrum of neurological and neuropsychiatric conditions. While intracranial...
Source: Frontiers in Pharmacology - May 12, 2022 Category: Drugs & Pharmacology Source Type: research

Highlighting the role of cognitive and brain reserve in the substance use disorder field.
CONCLUSION: CR and BR are variables not taken yet into account in drug addiction. However, they could give us a valuable information about people at risk, as well as patient's prognosis. PMID: 31204624 [PubMed - as supplied by publisher]
Source: Current Neuropharmacology - June 15, 2019 Category: Drugs & Pharmacology Authors: Cutuli D, de Guevara-Miranda DL, Castilla-Ortega E, Santín LJ, Sampedro-Piquero P Tags: Curr Neuropharmacol Source Type: research

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury
Conclusion In conclusion, our data demonstrate that mTBI causes late sensorial affective/cognitive deficiencies linked to altered neurotransmitter release at cortical level. Moreover, we showed that chronic CBD treatment reduces behavioral dysfunctions by restoring at least in part cortical biochemical processes. Taken together, our results suggest that CBD could represent a novel approach for the management of neuropsychiatric disorders associated with TBI. Author Contributions CB, LL, and RR conceived and designed the experiments. CB, MI, SB, FR, RI, and RM performed the experiments. GP, LS, SP, RR, LL, and IM analyze...
Source: Frontiers in Pharmacology - April 15, 2019 Category: Drugs & Pharmacology Source Type: research

Connecting Metainflammation and Neuroinflammation Through the PTN-MK-RPTP β/ζ Axis: Relevance in Therapeutic Development
Conclusion The expression of the components of the PTN-MK-RPTPβ/ζ axis in immune cells and in inflammatory diseases suggests important roles for this axis in inflammation. Pleiotrophin has been recently identified as a limiting factor of metainflammation, a chronic pathological state that contributes to neuroinflammation and neurodegeneration. Pleiotrophin also seems to potentiate acute neuroinflammation independently of the inflammatory stimulus while MK seems to play different -even opposite- roles in acute neuroinflammation depending on the stimulus. Which are the functions of MK and PTN in chronic neuroi...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Plant-Derived Alkaloids: The Promising Disease-Modifying Agents for Inflammatory Bowel Disease
Conclusion This paper summarizes the current findings regarding the anti-colitis activity of plant-derived alkaloids and shows how these alkaloids exhibit significant and beneficial effects in alleviating colonic inflammation. These natural alkaloids are not only promising agents for IBD treatment but are also components for developing new wonder drugs. However, the underlying molecular mechanisms or toxicological evaluation of most plant-derived alkaloids still require much scientific research, and their actual efficacies for IBD patients have not been verified well in field research. Thus, further clinical trials to elu...
Source: Frontiers in Pharmacology - April 11, 2019 Category: Drugs & Pharmacology Source Type: research

Executive (dys)function after stroke: special considerations for behavioral pharmacology
Stroke is a worldwide leading cause of death and long-term disability with concurrent secondary consequences that are largely comprised of mood dysfunction, as well as sensory, motor, and cognitive deficits. This review focuses on the cognitive deficits associated with stroke specific to executive dysfunction (including decision making, working memory, and cognitive flexibility) in humans, nonhuman primates, and additional animal models. Further, we review some of the cellular and molecular underpinnings of the individual components of executive dysfunction and their neuroanatomical substrates after stroke, with an emphasi...
Source: Behavioural Pharmacology - September 15, 2018 Category: Drugs & Pharmacology Tags: Review Articles Source Type: research

Roles of subunit phosphorylation in regulating glutamate receptor function.
Abstract Protein phosphorylation is an important mechanism for regulating ionotropic glutamate receptors (iGluRs). Early studies have established that major iGluR subtypes, including α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors and N-methyl-D-aspartate (NMDA) receptors, are subject to phosphorylation. Multiple serine, threonine, and tyrosine residues predominantly within the C-terminal regions of AMPA receptor and NMDA receptor subunits have been identified as sensitive phosphorylation sites. These distinct sites undergo either constitutive phosphorylation or activity-dependent phosphoryl...
Source: European Journal of Pharmacology - November 28, 2013 Category: Drugs & Pharmacology Authors: Wang JQ, Guo ML, Jin DZ, Xue B, Fibuch EE, Mao LM Tags: Eur J Pharmacol Source Type: research

Novel Approach to the Role of NMDA Receptors in Traumatic Brain Injury.
Abstract For more than two decades the intensive research effort on the role of NMDA receptors (NMDAR) in traumatic brain injury (TBI) and cerebral ischemia (stroke) was led by the observations that extracellular concentrations of glutamate and aspartate are elevated after the insult and play a major role in brain pathologies. Indeed, NMDAR antagonists were shown to improve post-injury recovery in animal models and subsequently, large scale placebo-controlled clinical trials in TBI and stroke were performed with NMDAR antagonists. However, all these trials have demonstrated either no benefit or even deleterious ef...
Source: CNS and Neurological Disorders Drug Targets - October 28, 2013 Category: Drugs & Pharmacology Authors: Shohami E, Biegon A Tags: CNS Neurol Disord Drug Targets Source Type: research

PPARs for Brain Disorders.
Abstract As is the case for any organ of the human body, the activity of the brain is continually kept in balance by precise hemostatic systems that modulate the main cellular metabolic pathways through complex multigenic regulatory programs. Peroxisome proliferator-activated receptors (PPARs) belong to the superfamily of nuclear receptors, which make them ligand-activated regulators of gene transcription [1]. There are currently three known subtypes of PPARs: PPARα, PPARβ (also described as PPARβ/δ or PPARδ) and PPARγ [2]. PPARs play fundamental roles in the regulation of key cell functions, including metab...
Source: Current Drug Targets - April 15, 2013 Category: Drugs & Pharmacology Authors: Rolland B, Bordet R Tags: Curr Drug Targets Source Type: research