CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 14, Issue 8, 2015

Disturbances in the circadian rhythms have long been associated with depression and mania. Animal models of mania and depression exhibit differential effects upon the intrinsic circadian period and the same occurs with antidepressants and mood stabilizers treatment. The intrinsic circadian period is expressed when there are no time clues or when the light/dark cycle length is beyond the capacity of synchronization Read More

Since most patients with schizophrenia do not respond properly to treatment, scientific effort has been driven to the development of new compounds acting on pharmacological targets beyond the dopaminergic system. Therefore, the aim is to review basic and clinical research findings from studies evaluating the effects of cannabidiol (CBD), an inhibitor of the reuptake and metabolism of anandamide and several other Read More

Nitric oxide is a gaseous neuromodulator that displays a core role in several neuronal processes. Beyond regulating the release of neurotransmitters, nitric oxide also plays a role in cell differentiation and maturation in the central nervous system. Although the mode of action of nitric oxide is not fully understood, it involves the activation of soluble guanylate cyclase as well as the nitration and S-nitrosylation of sp Read More

The dorsal periaqueductal gray (DPAG) has long been implicated in the pathophysiology of anxiety, particularly in panic disorder (PD). Evidence obtained with animal models indicates that different neurotransmitters/neuromodulators in this midbrain area are involved in the regulation of anxiety- (e.g. inhibitory avoidance) and panic- (e.g. escape) associated defensive behaviors. Earlier findings showed that activation of se Read More

Schizophrenia is a severe psychiatric disorder with a complex presentation comprising positive symptoms (e.g.: hallucinations and delusions), negative symptoms (e.g.: social withdrawal, blunted affect) and pervasive cognitive deficits that have been associated with functional decline. The pathophysiology of the disorder is equally complex, with abnormalities known to occur in the molecular, cellular, neurophysiological, and Read More

Since the first report that the mechanism of action of antidepressants involves the facilitation of monoaminergic neurotransmission in the brain in the 1960s, the leading hypothesis about the neurobiology of depression has been the so called “monoaminergic hypothesis”. However, a growing body of evidence from the last two decades also supports important involvement of non-monoaminergic mechanisms in the neurobiolog Read More

Preclinical studies have shown that phosphodiesterase inhibitors (PDE-Is) represent a potential pharmacological strategy for the treatment of brain ischemia sequelea. PDE-Is 3, 4 and 5 have been tested in several brain ischemia models. All the three PDE-Is after acute or chronic treatment decreased the degree of neurodegeneration and most of them improved functional recovery after brain injury by specific cellular and m Read More

Mutations in mitochondrial genes, oxidative insults, imbalance in redox mechanisms and dysregulated mitophagy are some of the leading causes for mitochondrial dysfunction and subsequent neurodegeneration in Parkinson’s disease. Targeting mitochondrial dysfunction and prolonging neuronal survival could potentially prove to be useful neuroprotective strategies. In some recent investigations, peroxisome proliferator Read More

Muscarinic acetylcholine receptors are stimulated by the neurotransmitter acetylcholine and are involved in various functions across the human body. These receptors have surfaced for their potential use as targets in treatment of Alzheimer’s disease. Muscarinic receptors have been reported to show binding interaction with various mamba toxins, such as dendrotoxins and muscarinic toxins that act as antagonists of t Read More

A dyshomeostasis of zinc ions has been reported for many psychiatric and neurodegenerative disorders including schizophrenia, attention deficit hyperactivity disorder, depression, autism, Parkinson’s and Alzheimer’s disease. Furthermore, alterations in zinc-levels have been associated with seizures and traumatic brain injury. Thus, altering zinclevels within the brain is emerging as a new target for the prevention and treatme Read More

The aggregation of α-synuclein (Syn or S) to form insoluble fibrils is important in the pathogenesis of Parkinson’s disease, but key risk factors remain ill-defined. We have developed Fluorescence Resonance Energy Transfer (FRET)-based assays for α-synuclein aggregation, using Green Fluorescent Protein variants Cerulean (C) or Venus (V), fused to each other (CV, VC) or to human synuclein (SC, SV etc). Bacterially expr Read More

Nerve growth factor (NGF) expression is augmented during neuroinflammation. However, its function in the dorsal root ganglia (DRG) and spinal cord (SC) during experimental autoimmune encephalomyelitis (EAE), the inflammatory model of Multiple Sclerosis, is indistinct. Thus, the role of antigenically induced NGF in Lewis rats under a state of EAE was considered. NGF mRNA and protein expression were highly increased in Read More

Chronic migraine (CM) is a disabling painful condition that is associated with dementia and thrombotic disease. It has been proposed that carbon monoxide (CO) and iron may play a role in CM, and CO and iron are products of the heme oxygenase system which is widespread within the brain. Further, CO and iron enhance plasmatic coagulation in part via a fibrinogen-dependent mechanism. Thus, our goal was to determine wh Read More

Schizophrenia is a neuropsychiatric disorder in which abnormalities in the prefrontal cortex lead to impaired synthesis of dopamine. It is associated with hallucination, psychosis and hearing impairments. Many susceptible genes have been identified in schizophrenia such as catechol-O-methyltransferase (COMT) and serine/threonine kinase (AKT1). Single nucleotide polymorphisms (SNPs) in these genes have not been id Read More

Recently, microRNAs (miRNAs) are emerging as new regulators in the pathogenesis of temporal lobe epilepsy (TLE) and playing a major role in the inflammatory and immune processes. The aim of the present study was to evaluate the dynamic expression of brain-specific miR-183 and miR-135a, brain-enriched miR-125b and miR-128 and inflammation-related miR-30c and miR-27a. Status epilepticus evoked by pilocarpine ad Read More