CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 12, Issue 8, 2013

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disease with worldwide increasing incidence. PD is the second most prevalent neurodegenerative disease and the first that involves motor symptoms. The great majority of cases, defined as sporadic with non-familial disease, show a highly variable risk of disease due to environmental and genetic factors that remain largely unknown. Furthermore, the Read More

Pathological aggregation of alpha-synuclein as Lewy-bodies and neurites is a hallmark of a group of neurodegenerative disorders named alpha-synucleinopathies. It is becoming apparent that alpha-synuclein facilitates presynaptic neuronal function in the brain, and events leading to its aggregation produce marked disruption of neurotransmitter release mechanism. We discuss here the literature related to the function o Read More

Parkinson’s disease (PD) and L-DOPA-induced dyskinesia, a major complication of treatment of PD, are associated with molecular and functional alterations occurring into the medium spiny neurons (MSNs) of the dorsal striatum, a key areas involved in the control of motor activity. MSNs are regulated by several neurotransmitter systems including dopamine, glutamate and adenosine via activation of distinct receptors. Increa Read More

A critical step in the development of effective therapeutics to treat Parkinson’s disease (PD) is the identification of molecular pathogenic mechanisms underlying this chronically progressive neurodegenerative disease. However, while animal models have provided valuable information about the molecular basis of PD, the lack of faithful cellular and animal models that recapitulate human pathophysiology is delaying the Read More

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson’s disease (PD) has Read More

We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the androgen receptor. SBMA was the first polyglutamine disease to be discovered, and we compare and contrast it with related degenerative disorders of the nervous system caused by expanded glutamine tracts. We review the cellular and animals Read More

Research on the FKBP5 gene and FKBP51 protein has more than doubled since the discovery that polymorphisms in this gene could alter treatment outcomes and depressive behavior in humans. This coincided with other data suggesting that the stress hormone axis contributes to the development of numerous mental illnesses. As a result, FKBP51 now lies at the heart of the research of many stress related psychiatric Read More

The most relevant biological action of aldosterone in epithelial tissues is the regulation of sodium reabsorption through binding to the mineralocorticoid receptor (MR). Glucocorticoids also bind with high affinity to MR, which is usually protected by the enzyme 11β-hydroxysteroid dehydrogenase. This activity prevents MR activation by cortisol despite the large prevalence of this steroid in plasma. Nonetheless, ther Read More

Isolation of glucocorticoids (GCs) from adrenal glands followed by synthesis led rapidly to their first clinical application, about 70 years ago, for treatment of rheumatoid arthritis. To this day GCs are used in diseases that have an inflammatory component. However, their use is carefully monitored because of harmful side effects. GCs are also synonymous with stress and adaptation. In CNS, GC binds and activates high aff Read More

In recent years, it has been established that environmental stress leaves enduring traces at distinct sites on the chromatin, accompanied by permanent alterations of gene transcription. This process depends on duration and extent of the discharge of stress hormones. Here, we aimed at identifying genes that are both regulated by the glucocorticoid receptor (GR) and display epigenetic features of transcriptional control. Read More

Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone receptors, the modulation of intracellular signalling cascades and the interaction of prog Read More

The gonadal steroid 17β-estradiol (E2) has shown powerful cytoprotective effect on cells. In addition to classical genomic mechanisms of action, E2 also exerts non-classical effects on intracellular signal transduction. Extensive studies during the past two decades have provided evidence that the E2-induced non-classical signaling on second messenger molecules plays a critical role in the neuroprotective effect of E2. These observ Read More

Due to its efficacy and acceptability, paroxetine is situated in the top ten of drugs prescribed for the treatment of major depression and essentially all anxiety disorders. Adults under paroxetine treatment report relief after 4-6 weeks of administration; furthermore, this drug can be prescribed for periods lasting longer than one year. Therefore, paroxetine treatment has a pattern of ingestion that is mainly chronic rather than a Read More

The major neuropathologic hallmarks in Alzheimer's disease (AD) consist of neuronal cell loss in selected brain regions, as well as deposition of extracellular senile plaques and intracellular neurofibrillary tangles. Further to these lesions, neuroinflammation is a feature of AD pathology and is thought to contribute to the neurodegeneration. Inflammation clearly occurs in pathologically vulnerable regions of the AD brain, with in Read More

Multiple sclerosis (MS) is a chronic disease resulting from targeted destruction of central nervous system (CNS) myelin. MS is suggested to be an autoimmune disease involving the pathogenic activation of CD4+ T cells by a foreign antigen in the peripheral blood. The activated CD4+ T cells liberate inflammatory cytokines that facilitate the breakdown of the blood-brain barrier (BBB) promoting their passage into the CNS. Insi Read More

Evaluation of potential analgesic therapeutics and the elaboration of the neurobiology of pain have heavily relied on pain models developed in rodents. However, a limitation of rodents is their phylogenetic distance from humans, which could in part account for the failure of some preclinical findings to translate to clinical utility. By contrast, given their genetic closeness and phenotypic similarities to humans, it is suggested tha Read More

The blood-brain barrier significantly impedes treatment of central nervous system disorders by preventing drug entry into the brain. Several strategies have been developed to overcome this problem, but progress has been hampered due to a lack of efficacious drug delivery systems (DDS). Now, owing to DDS, therapeutic compounds can be transported to the site of action and accumulate there. This modern approac Read More