In one study, Susan Hayflick of Oregon Health Sciences University, Bing Zhou of the University of California in San Francisco, and their colleagues identify the gene and the mutation responsible for Hallervorden-Spatz syndrome (HSS), a disease wherein iron accumulates in the basal ganglia. Although no causal link has been shown between the accumulated iron and the gradual motor and intellectual deterioration that characterizes HSS, Hayflick's group offers a candidate for further research. They have identified a novel gene (dubbed PANK2) that codes for the enzyme pantothenate kinase, and have determined that defects in PANK2 underlie HSS. They hypothesize that the link between neuronal damage and excessive iron in HSS may be that the defective PANK2 protein product fails to tie up sufficient quantities of cysteine. This amino acid can be turned into an oxidative radical-already demonstrated to be neurotoxic-by its interactions with iron. Hayflick and colleagues point out that disturbed cysteine metabolism has been implicated in both Alzheimer's and Parkinson's diseases.

Another mechanism whereby iron could harm neurons is suggested by the work of John Burn and Andrew Curtis of the Institute of Human Genetics in Newcastle upon Tyne and their colleagues. These researchers have discovered a new neurodegenerative disorder, which they term "neuroferritinopathy," traceable to a mutation in one of the two subunits of ferritin. Ferritin is an iron-storage molecule, and an obvious possibility is that the mutant form of the ferritin molecule binds less iron for long-term storage. In an accompanying News and Views article, Tracey Rouault of the National Institute of Child Health and Human Development (USA) discusses how the peculiar polar structure of the neuron (dendrites and axons bridging distant synapses and cell bodies) might lend itself to damage from unstable ferritin-iron complexes.-Hakon Heimer.

Reference:(1) Curtis AR, Fey C, Morris CM, Bindoff LA, Ince PG, Chinnery PF, Coulthard A, Jackson MJ, Jackson AP, McHale DP, Hay D, Barker WA, Markham AF, Bates D, Curtis A, Burn J. Mutation in the gene encoding ferritin light polypeptide causes dominant adult-onset basal ganglia disease. Nat Genet. 2001 Aug;28(4):350-4. Abstract

(2) Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet 2001 Aug;28(4):345-9. Abstract

(3) Rouault TA. Iron on the brain. Nat Genet 2001 Aug;28(4):299-300. Abstract