CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 10, Issue 6, 2011

Post-transcriptional regulation represents a powerful means to exert control over gene expression and to enhance plasticity and adaptability at the molecular, cellular and functional levels, even in a complex organ such as the nervous system. Approximately 80% of the human brain genome is transcribed into RNA, yet only about 2% of the genome is transcribed into protein, which emphasizes the capability of various steps of R Read More

As a relatively common neurodegenerative disease associated with aging, Parkinson's disease (PD) impacts increasing numbers of people as population structures are shifted towards older individuals. For many people living with PD, the disease process leads progressively to increased disability and lowered quality of life. Many of the cardinal symptoms in PD relate to impairment of normal fluid movement, but as the dis Read More

A promising target for improved therapeutics in Parkinson's disease is the nicotinic acetylcholine receptor (nAChR). nAChRs are widely distributed throughout the brain, including the nigrostriatal system, and exert important modulatory effects on numerous behaviors. Accumulating evidence suggests that drugs such as nicotine that act at these sites may be of benefit for Parkinson's disease treatment. Recent work indicates t Read More

Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A2A receptors (A2ARs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such us the dopamine D2 receptor (D2R). Furthermore, it is assumed that the formation of balanced A2AR/D2R receptor oligomers are Read More

Dyskinesia and motor fluctuations affect up to 90% of patients with Parkinson's disease (PD) within ten years of L-DOPA pharmacotherapy, and represent a major challenge to a successful clinical management of this disorder. There are currently two main treatment options for these complications, namely, deep brain electrical stimulation or continuous infusion of dopaminergic agents. The latter is achieved using eith Read More

There has been renewed interest in the surgical treatment of Parkinson's disease (PD) over the past 20 years. In the 1940's to 1960's many PD patients underwent neurosurgical procedures to ablate specific brain targets to alleviate tremor and, to a lesser extent, akinesia and rigidity. With the introduction of levodopa in the 1960s, and the realization of its striking benefits, surgical treatment of movement disorders virtually Read More

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive procedure whereby a pulsed magnetic field stimulates electrical activity in the brain. Parkinson's disease (PD) is a neurodegenerative process characterized by numerous motor and nonmotor clinical manifestations for which effective, mechanism-based treatments remain elusive. Consequently, more advanced non-invasive therapeutic methods are required. Read More

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor dysfunction that occurs secondary to loss of dopaminergic neurons in the nigrostriatal pathway. Current pharmacotherapies focus on the replacement of lost dopamine to alleviate disease symptoms. However, over time this method of therapy loses effectiveness due to the continued death of dopaminergic neurons. Alterna Read More

One of the critical issues in Parkinson disease (PD) research is the identity of the specific toxic, pathogenic moiety. In PD, mutations in alpha-synuclein (αsyn) or multiplication of the SNCA gene encoding αsyn, result in a phenotype of cellular inclusions, cell death, and brain dysfunction. While the historical point of view has been that the macroscopic aggregates containing αsyn are the toxic species, in the last several ye Read More

Intense research efforts are currently directed at elucidating the etiology of Parkinson's disease (PD). One approach that has begun to shed light on the PD pathogenic pathways is the identification of disease genes through genetic linkage or association studies. These studies have revealed that several kinases may be involved in PD, as some PD genes encode kinases themselves while other PD genes are found in the same cellul Read More

Stroke causes a devastating insult to the brain resulting in severe neurological deficits because of a massive loss of different neurons and glia. In the United States, stroke is the third leading cause of death. Stroke remains a significant clinical unmet condition, with only 3% of the ischemic patient population benefiting from current treatment modalities, such as the use of thrombolytic agents, which are often limited by a na Read More

Multiple sclerosis (MS) is a chronic disease of the central nervous system with not yet completely understood pathogenesis. The so called “chronic cerebrospinal venous insufficiency (CCSVI) theory” has recently emerged, supporting the concept of a cerebrospinal venous drainage impairment as the cause of MS. Since the first publication on this topic with a claimed 100% specificity and sensitivity of the condition for MS diagnos Read More