Neuroreport · 1998 · 89 citations · 9 references
Life SciencesGeneticsMolecular BiologyDna RepairMolecular NeuroscienceNeurodegenerationAmyotrophic Lateral SclerosisDna Repair DefectsMolecular Basis Of NeurodegenerationMolecular NeurogeneticsNeurodegenerative DiseasesNeurodegenerative DisordersAbasic SitesAmyotrophic Lateral Sclerosis PathologyDna Repair MechanismsDna Repair Pathway DefectsMissense MutationsOxidative Dna DamageOxidative Dna Damage Repair DefectsOxidative Dna Lesions
Among the more frequent oxidative DNA injuries is the formation of abasic sites (AP sites) resulting from removal of purine or pyrimidine bases, estimated to occur at a rate of 1 x 10(4)/genome/24 h. A defect in DNA repair at this level could account for the accumulation of mutations and subsequent genome instability. We have identified missense mutations in the APE gene coding for a multifunctional DNA repair enzyme, AP endonuclease in eight of 11 patients with amyotrophic lateral sclerosis (ALS) and familial ALS. These mutations could affect the repair of abasic sites leading to the accumulation of mutations in neurons, resulting in their degeneration and death. Our findings implicate mutated AP endonuclease in the pathogenesis of ALS.
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