Journal of Inherited Metabolic Disease

, Volume 28, Issue 6, pp 1055–1064 | Cite as

Dietary rescue of fumble—a Drosophila model for pantothenate-kinase-associated neurodegeneration

Article

Summary

Hallervorden–Spatz syndrome (HSS) is a devastating neurological disease, characterized by iron accumulation in the globus pallidus in the basal ganglia. Most HSS cases are caused by mutations in one of the four human pantothenate kinases (PANK2). This PANK2-caused subgroup of HSS is sometimes referred as PKAN (pantothenate-kinase-associated neurodegeneration). No effective treatment for PKAN or HSS is currently available. fumble, a Drosophila mutant that carries a mutation in Drosophila Pank, has many features similar to those of PKAN patients. In this study, we used fumble as a model to evaluate various compounds or nutritional products for their possible therapeutic efficacy. While no product was found to dramatically improve the symptoms, GKE (containing Ginkgo biloba extract and flavone) and vitamin E showed statistically significant beneficial effects. Our studies indicate that pantothenate is of limited value in alleviating fumble phenotypes and also suggest that some compounds might have deleterious effects.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Afshar K, Gonczy P, DiNardo S, Wasserman SA (2001) fumble encodes a pantothenate kinase homolog required for proper mitosis and meiosis in Drosophila melanogaster. Genetics 157: 1267–1276.PubMedGoogle Scholar
  2. Ching KH, Westaway SK, Gitschier J, Higgins JJ, Hayflick SJ (2002) HARP syndrome is allelic with pantothenate kinase-associated neurodegeneration. Neurology 58: 1673–1674.PubMedGoogle Scholar
  3. Hayflick SJ, Westaway SK, Levinson B, et al (2003) Genetic, clinical, and radiographic delineation of Hallervorden–Spatz syndrome. N Engl J Med 348: 33–40.CrossRefPubMedGoogle Scholar
  4. Hofferberth B (1989) The effect of Ginkgo biloba extract on neurophysiological and psychometric measurement results in patients with psychotic organic brain syndrome. A double-blind study against placebo. Arzneimittelforschung 39: 918–922.PubMedGoogle Scholar
  5. Hortnagel K, Prokisch H, Meitinger T (2003) An isoform of hPANK2, deficient in pantothenate kinase-associated neurodegeneration, localizes to mitochondria. Hum Mol Genet 12: 321–327.CrossRefPubMedGoogle Scholar
  6. Houlden H, Lincoln S, Farrer M, Cleland PG, Hardy J, Orrell RW (2003) Compound heterozygous PANK2 mutations confirm HARP and Hallervorden–Spatz syndromes are allelic. Neurology 61: 1423–1426.PubMedGoogle Scholar
  7. Johnson MA, Kuo YM, Westaway SK, et al (2004) Mitochondrial localization of human PANK2 and hypotheses of secondary iron accumulation in pantothenate kinase-associated neurodegeneration. Ann NY Acad Sci 1012: 282–298.PubMedGoogle Scholar
  8. Kotzbauer PT, Truax AC, Trojanowski JQ, Lee VM (2005) Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2. J Neurosci 25: 689–698.CrossRefPubMedGoogle Scholar
  9. Kuo YM, Duncan JL, Westaway SK, et al (2005) Deficiency of pantothenate kinase 2 (Pank2) in mice leads to retinal degeneration and azoospermia. Hum Mol Genet 14: 49–57.Google Scholar
  10. Min KT, Benzer S (1999) Preventing neurodegeneration in the Drosophila mutant bubblegum. Science 284: 1985–1988.Google Scholar
  11. Polich J, Gloria R (2001) Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Hum Psychopharmacol 16: 409–416.PubMedGoogle Scholar
  12. Quaranta L, Bettelli S, Uva MG, Semeraro F, Turano R, Gandolfo E (2003) Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology 110: 359–362.CrossRefPubMedGoogle Scholar
  13. Tarnopolsky MA, Beal MF (2001) Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders. Ann Neurol 49: 561–574.CrossRefPubMedGoogle Scholar
  14. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ (2001) A novel pantothenate kinase gene (PANK2) is defective in Hallervorden–Spatz syndrome. Nature Genetice 28: 345–349.Google Scholar

Copyright information

© SSIEM and Springer 2005

Authors and Affiliations

  1. 1.Department of Biological Sciences and BiotechnologyTsinghua UniversityBeijingChina
  2. 2.Howard Hughes Medical InstituteUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations