HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pantothenate kinase-associated neurodegeneration.

Abstract
Pantothenate kinase-associated neurodegeneration (PKAN) is a hereditary progressive disorder and the most frequent form of neurodegeneration with brain iron accumulation (NBIA). PKAN patients present with a progressive movement disorder, dysarthria, cognitive impairment and retinitis pigmentosa. In magnetic resonance imaging, PKAN patients exhibit the pathognonomic "eye of the tiger" sign in the globus pallidus which corresponds to iron accumulation and gliosis as shown in neuropathological examinations. The discovery of the disease causing mutations in PANK2 has linked the disorder to coenzyme A (CoA) metabolism. PANK2 is the only one out of four PANK genes encoding an isoform which localizes to mitochondria. At least two other NBIA genes (PLA2G6, C19orf12) encode proteins that share with PANK2 a mitochondrial localization and all are suggested to play a role in lipid homeostasis. With no causal therapy available for PKAN until now, only symptomatic treatment is possible. A multi-centre retrospective study with bilateral pallidal deep brain stimulation in patients with NBIA revealed a significant improvement of dystonia. Recently, studies in the PANK Drosophila model "fumble" revealed improvement by the compound pantethine which is hypothesized to feed an alternate CoA biosynthesis pathway. In addition, pilot studies with the iron chelator deferiprone that crosses the blood brain barrier showed a good safety profile and some indication of efficacy. An adequately powered randomized clinical trial will start in 2012. This review summarizes clinical presentation, neuropathology and pathogenesis of PKAN.
AuthorsMonika B Hartig, Holger Prokisch, Thomas Meitinger, Thomas Klopstock
JournalCurrent drug targets (Curr Drug Targets) Vol. 13 Issue 9 Pg. 1182-9 (Aug 2012) ISSN: 1873-5592 [Electronic] United Arab Emirates
PMID22515741 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Phosphotransferases (Alcohol Group Acceptor)
  • pantothenate kinase
Topics
  • Animals
  • Humans
  • Mice
  • Mice, Transgenic
  • Neurodegenerative Diseases (drug therapy, enzymology, genetics)
  • Phosphotransferases (Alcohol Group Acceptor) (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: