Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nephronophthisis is a common genetic cause of end-stage renal disease in childhood. Recently, Invs was identified as the gene mutated in the infantile form of nephronophthisis. Humans with nephronophthisis develop a large number of extrarenal manifestations, including situs variations, anomalies of the hepatobiliary system, retinal degeneration and cerebellar ataxia. Mice homozygous for a mutation in the Invs gene (inv mouse) die during the first week after birth as a result of renal and liver failure. Although organ anomalies have been characterized in human nephronophthisis and the inv mouse, little is known about the tissue expression of the Invs gene product, inversin. We have used laser confocal microscopy of paraffin-embedded murine tissue sections to provide the first detailed characterization of the distribution of inversin in various organs. Our results show that inversin is localized to distal tubules in the kidney, hepatic bile ducts, acinar and ductal pancreatic cells, epithelial intestinal cells, splenic germinal centres, bronchiolar epithelial cells, dendrites of cerebellar Purkinje cells, retinal neural cells and spermatocytes and spermatids in the testis. The localization of inversin in distal tubules in the kidney and in extrarenal tissues suggests that the expression of this protein has an important function in a variety of organs. Further studies are required to understand the way in which mutations in the Invs gene lead to the multi-organ pathology of inv mouse and human nephronophthisis.
 ...
PMID:Differential tissue distribution of the Invs gene product inversin. 1600 6

An overview of the current pharmacotherapy of central vestibular syndromes and the most common forms of central nystagmus as well as cerebellar disorders is given. 4-aminopyridine (4-AP) is recommended for the treatment of downbeat nystagmus, a frequent form of acquired persisting fixation nystagmus, and upbeat nystagmus. Animal studies showed that this non-selective blocker of voltage-gated potassium channels increases Purkinje cell excitability and normalizes the irregular firing rate, so that the inhibitory influence of the cerebellar cortex on vestibular and deep cerebellar nuclei is restored. The efficacy of 4-AP in episodic ataxia type 2, which is most often caused by mutations of the PQ-calcium channel, was demonstrated in a randomized controlled trial. It was also shown in an animal model (the tottering mouse) of episodic ataxia type 2. In a case series, chlorzoxazone, a non-selective activator of small-conductance calcium-activated potassium channels, was shown to reduce the DBN. The efficacy of acetyl-DL-leucine as a potential new symptomatic treatment for cerebellar diseases has been demonstrated in three case series. The ongoing randomized controlled trials on episodic ataxia type 2 (sustained-release form of 4-aminopyridine vs. acetazolamide vs. placebo; EAT2TREAT), vestibular migraine with metoprolol (PROVEMIG-trial), cerebellar gait disorders (sustained-release form of 4-aminopyridine vs. placebo; FACEG) and cerebellar ataxia (acetyl-DL-leucine vs. placebo; ALCAT) will provide new insights into the pharmacotherapy of cerebellar and central vestibular disorders.
...
PMID:Update on the pharmacotherapy of cerebellar and central vestibular disorders. 2708 81