CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 13, Issue 4, 2014

Traumatic brain injury causes progressive neurodegeneration associated with chronic microglial activation. Recent studies show that neurodegeneration and neuroinflammation after traumatic brain injury can be inhibited as late as one month in animals by the activation of the metabotropic glutamate receptor 5 in microglia using (RS)-2-chloro-5- hydroxy-phenylglycine. However, the therapeutic potential of this Read More

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 subseque Read More

The role of the 18-kDa Translocator Protein (TSPO) in cell death induced by NH4Cl (1-50 mM) for 24-72 hours to human glioblastoma U118MG cells was investigated. Cell death was already observed after 48 hours of treatment with NH4Cl at 5 mM. Dose and time-responses curves indicated that 15 mM of NH4Cl applied for 72 hours was the optimal condition for our viability assays. For example, 72 hours of 15 mM of NH4Cl cause Read More

Alzheimer’s disease (AD) is the most common form of dementia occurring in the elderly. Several hypotheses have been proposed to explain the pathophysiology of AD, including amyloidogenesis, disruption of calcium homeostasis, energetic failure, induction of oxidative stress, and hyperphosphorylation of tau protein. This review examines associations between cellular and subcellular injuries, neurodegeneration, an Read More

Traumatic brain injury (TBI) is still the worldwide, leading cause of mortality and morbidity in young adults. The prognosis of TBI patients is strongly affected by secondary brain damage including mitochondrial dysfunctions. In many basic and clinical studies, mitochondrial dysfunctions, including the opening of mitochondrial permeability transition (mPT) pore, and treatments including cyclosporine A (CsA) have been studied. Thes Read More

Traumatic brain injuries represent the leading cause of death and morbidity in young adults in western countries, and are responsible for a major social and economical burden. For decades, the mainstay of neurotrauma management has been represented by control of post-traumatic edema. With the emergence of a better understanding of the underlying cellular mechanisms responsible for the generation of secondary brain Read More

Accumulation of α-synuclein is key to the pathogenesis of Parkinson's disease (PD), though the exact mechanisms involved in its toxicity are still subject to debate. Increased α-synuclein expression or reduced degradation may play a role in the proteotoxicity observed in PD. Here we review the mechanisms of α-synuclein ubiquitination by different E3 ubiquitin-ligases, and its degradation via the proteasome, autophagy and ly Read More

The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, resp Read More

Glatiramer acetate (GA) is one of the most widely used disease-modifying drugs for the treatment of relapsingremitting multiple sclerosis; is assumed to have inductor effects on neurotrophic factor expression. One of these neurotrophic factor systems is the brain-derived neurotrophic factor (BDNF)/receptor tyrosine kinase B (TrkB) pathway. Peripheral blood is thought to contain soluble BDNF, and some blood cells expr Read More

The systematical associations between stroke and coronary heart disease (CHD) remain controversial and uncertain. Network construction and modularized analysis have become powerful tools in the field of systems biology research, which can help us to mine the multidimensional characters of correlation between the two diseases in depth. A total of 218 stroke-related and 204 CHD-related genes were identified vi Read More

Multidrug resistance mediated by over-expression of P-glycoprotein (P-gp) in brain is an important mechanism accounting for the drug-therapy failure in epilepsy. Over-expression of P-gp in epilepsy rat brain may be regulated by inflammation and nuclear factor-kappa B (NF-κB) activation. Inhibitory κ B kinase subunit β (IKKβ) is an up-stream molecular controlling NF-κB activation. With the small interfering RNA (siRNA) tech Read More

Depressive disorders have, for a sizeable extent, proven resilient to pharmacotherapy. Established drugs such as selective serotonin reuptake inhibitors (SSRIs) or serotonin-noradrenaline reuptake inhibitors (SNRIs) often provide inadequate symptom relief and sometimes fail altogether. Recently, interest in antidepressant effects of scopolamine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, has a Read More

The purpose of the study was to evaluate the potential effects of Citrus reticulate (mandarin) peel methanolic extract (MPME) on memory dysfunction in rats. Memory impairment was produced by scopolamine (1.4 mg/kg, intraperitoneally injected). Brain acetylcholinesterase enzyme (AChE) activity was measured to assess the central cholinergic activity. This study also investigated the effect of scopolamine on norepin Read More

Alzheimer’s disease (AD) represents a neurological disorder, which is caused by enzymatic degradation of an amyloid precursor protein into short peptide fragments that undergo association to form insoluble plaques. Preliminary studies suggest that cyanobacterial extracts, especially the light-harvesting protein phycocyanin, may provide a means to control the progression of the disease. However, the molecular mechanism of Read More

Mental retardation (MR)/ intellectual disability (ID) is a neuro-developmental disorder characterized by a low intellectual quotient (IQ) and deficits in adaptive behavior related to everyday life tasks such as delayed language acquisition, social skills or self-help skills with onset before age 18. To date, a few genes (PRSS12, CRBN, CC2D1A, GRIK2, TUSC3, TRAPPC9, TECR, ST3GAL3, MED23, MAN1B1, NSUN1) for autosomal-recessiv Read More

Introduction: Parkinson’s disease (PD) is one of the most common neurodegenerative diseases, and PD patients can present a variety of comorbidities that increase with age. Among them, cardiovascular and cerebrovascular diseases are the most prominent. Aim: To assess the cardiovascular and cerebrovascular profiles of PD patients. Patients and Methods: The cardiovascular risk factors of 126 PD patients wer Read More

Prolonged exposure to volatile anesthetics alone may be detrimental to the brain. However, volatile anesthetics, such as isoflurane, can provide neuroprotection against various damaging insults. Application of isoflurane after focal brain ischemia reduces ischemic brain injury. We determined whether this isoflurane postconditioning-induced neuroprotection requires inhibition of brain ischemia-induced Notch signaling activation Read More