CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 16, Issue 3, 2017

Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-ter Read More

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with prominent motor and non-motor symptoms. Psychosis develops in over 40% of PD patients and it is one of the most distressing symptoms for patients and caregivers alike. Until recently, atypical antipsychotics, clozapine and quetiapine were used to treat psychotic symptoms, but treatment was associated with substantial concerns for side-effects of cloza Read More

Heat shock proteins (HSPs) are families of molecular chaperones that play important homeostatic functions in the central nervous system (CNS) by preventing protein misfolding, promoting degradation of improperly folded proteins, and protecting against apoptosis and inflammatory damage especially during hyperthermia, hypoxia, or oxidative stress. Under stress conditions, HSPs are upregulated to protect cells from damag Read More

Purinergic signalling, i.e. ATP as an extracellular signalling molecule and cotransmitter in both peripheral and central neurons, is involved in the physiology of neurotransmission and neuromodulation. Receptors for purines have been cloned and characterised, including 4 subtypes of the P1(adenosine) receptor family, 7 subtypes of the P2X ion channel nucleotide receptor family and 8 subtypes of the P2Y G protein-couple Read More

In this article the emerging biological overlaps of CNS disorders and psychiatric conditions are reviewed. Recent work has highlighted how immune-inflammatory processes and their interactions with oxidative and nitrosative stress, couple to drive changes in neuroregulatory tryptophan catabolites, with consequences for serotonin availability, including as a precursor for the melatonergic pathways. Subsequent alterations Read More

The blood brain barrier (BBB) is a continuous, non-fenestrated vessel system that tightly regulates the movement of molecules, ions, and cells between the blood and the central nervous system. Endothelial cells are the major constituents of the BBB and these cells are linked to each other through intercellular contact points composed of tight junctions, adherent junctions and gap junctions. These three types of junctions ar Read More

Effective non-genetic disease modifying treatments for Huntington’s disease (HD) will necessarily target multiple diverse neurodegenerative processes triggered by mutant huntingtin. Neurotrophin receptors are well-positioned for this task as they regulate signaling pathways that largely overlap with signaling networks contributing to HD-related synaptic dysfunction, glial activation, excitotoxicity, and other degenerative p Read More

Neuropathic pain is a chronic neurological disorder affecting millions of people around the world. The currently available pharmacologic agents for the treatment of neuropathic pain have limited efficacy and are associated with dose related unwanted adverse effects. Due to the limited access of drug molecules across blood-brain barrier, a small percentage of drug that is administered systematically, reaches the central nervou Read More

It is currently known that erythrocytes are the major source of sphingosine 1-phosphate (S1P) in the body. S1P acts both extracellularly as a cellular mediator and intracellularly as an important second messenger molecule. Its effects are mediated by interaction with five specific types of G proteincoupled S1P receptor. Fingolimod, is a recognized modulator of S1P receptors, and is the first orally active disease-modifying the Read More

Central nervous system diseases are major health issues and are often associated with disability or death. Most central nervous system disorders are characterized by high levels of oxidative stress. Nuclear factor erythroid 2 related factor (Nrf2) is known for its ability to regulate the expression of a series of enzymes with antioxidative, prosurvival, and detoxification effects. Under basal conditions, Nrf2 forms a complex with Kelc Read More

Background: Cerebrospinal-fluid (CSF) Alzheimer’s Disease (AD) biomarkers have been extensively studied in Parkinson’s Disease (PD). Although reduced CSF beta-amyloid1-42 (Aβ42) levels have been associated with cognitive decline in PD, the alteration of CSF tau proteins remains controversial. In addition, the impairment of the blood-brain barrier (BBB) has been previously demonstrated along the PD progression. Read More

Purpose: To investigate the effect of curcumin on tumor growth and angiogenesis of human gliomas and identify the underlying molecular mechanisms. Methods: A mouse xenograft glioma model was established by subcutaneously inoculating tumor cell aggregates derived from the U87 cell line. Mice were treated with 0.01ml/g body weight of curcumin or saline. Tumor volume was measured. Microvessel density was Read More

Background: Oxidative stress and amyloid deposition are tightly interconnected pathological features of Alzheimer disease. In this respect, both amyloid production and aggregation may be stimulated by oxidative stress and also the increase of pathogenic β-amyloid and its aggregated form lead to oxidative stress progression. Therefore, the search for potential drugs with both antioxidant and antiaggregation properties are Read More

Background: Motoneurons with naturally elevated calcium binding protein content, such as parvalbumin, are more resistant against injury. Furthermore, increase of intracellular calcium, which plays a pivotal role in injury of neurons, could be moderated by elevating their calcium binding proteins. Objective: To test whether by elevating parvalbumin content of motoneurons, activation of neighboring microglial cells, a robus Read More