Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malfunction in ion channels, due to mutations in genes encoding channel proteins or the presence of autoantibodies, are increasing being implicated in causing disease conditions, termed channelopathies. Dysfunction of potassium (K(+)) channels has been associated with the pathophysiology of a number of neurological, as well as peripheral, disorders (e.g., episodic ataxia, epilepsy, neuromyotonia, Parkinson's disease, congenital deafness, long QT syndrome). K(+) channels, which demonstrate a high degree of diversity and ubiquity, are fundamental in the control of membrane depolarisation and cell excitability. A common feature of K(+) channelopathies is a reduction or loss of membrane potential repolarisation. The identification of K(+) channel subtype specific openers will allow the recovery of the mechanism(s) responsible for counteraction of uncontrolled cellular depolarisation. Synthetic agents that demonstrate K(+) channel opening properties are available for a variety of K(+) channel subtypes (e.g., K(ATP), BK(Ca), GIRK and M-channel). This study reviews the realistic therapeutic potential that may be gained in a broad spectrum of clinical conditions by K(+) channel openers. K(+) channel openers would therefore identify dysfunctional K(+) channel as therapeutic targets for clinical benefit, in addition being able to modulate normally functioning K(+) channels to gain clinical management of pathophysiological events irrespective of the cause.
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PMID:Is there a role for potassium channel openers in neuronal ion channel disorders? 1106 Aug 6

The use of specific activators and inhibitors that penetrate the central nervous system has suggested an essential functional role of L-type calcium channels (LTCC) in several important physiological processes of the brain, including the modulation of the mesoaccumbal dopamine signalling pathway, synaptic transmission of auditory stimuli and synaptic plasticity of neutral and aversive learning and memory processes. However, the lack of selectivity of available pharmacological agents towards the most prominent LTCC isoforms in the brain, namely Cav1.2 and Cav1.3, has hampered the elucidation of the precise contribution made by each specific channel isoform within these specific physiological processes. Modern genetic approaches, both in rodents and in human, have recently enhanced our understanding of the selective functional roles of Cav1.2 and Cav1.3 channels. In rodents, the characterisation of global and conditional isoform-specific knockouts suggests a contribution of Cav1.2 channels in spatial memory formation, whereas Cav1.3 channels seem to be involved in the consolidation of fear memories and in neurodegenerative mechanisms associated with the development of Parkinson's disease. With regard to the molecular mechanisms underlying drug addiction, Cav1.3 channels are necessary for the development and Cav1.2 channels for the expression of cocaine and amphetamine behavioural sensitisation. In humans, both the identification of naturally occurring LTCC variants ("channelopathies") and unbiased genome-wide association studies have linked LTCCs to working memory performance in healthy individuals and schizophrenic patients. Individually, CACNA1C polymorphisms and CACNA1D variants have been linked to a variety of psychiatric diseases and to congenital deafness, respectively. However, the contribution of individual LTCCs and their polymorphisms to human brain function and diseases remains unclear, necessitating the use of isoform-specific pharmacological agents.
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PMID:The role of L-type voltage-gated calcium channels Cav1.2 and Cav1.3 in normal and pathological brain function. 2499 99