Modulation of Parkinson’s Disease Associated Protein Rescues Alzheimer’s Disease Degeneration

: DJ-1, a causative gene product of an autosomal recessive familial form of Parkinson's disease (PD), plays roles in reducing oxidative stress and transcriptional regulation. Loss of its function is thought to result in the onset of PD. DJ-1 has been demonstrated to show general cytoprotective function mainly through antioxidant properties and possibly regulates the extent of stroke-induced damage and neurodegeneration in Alzheimer's disease (AD). The paper, "Effects of a DJ-1-Binding Compound on Spatial Learning and Memory Impairment in a Mouse Model of Alzheimer's Disease", by Kitamura et al. in this issue of Journal of Alzheimer's Disease reports that a DJ-1 modulator UCP0054278/compound B (comp-B), which has been previously shown to exhibit antioxidant and neuroprotective properties in PD models, can prevent neurodegenerative changes and cognitive dysfunction in an animal model of AD. Indeed, comp-B reduces not only α-synuclein but also insoluble Aβ42 levels, prevents the reductions in synaptophysin and drebrin, and rescues cognitive deficits in transgenic APdE9 mice model of AD. It is noteworthy that pharmacological modulation of a familial PD gene product is sufficient to modify biochemical phenotypes and cognitive performance in amyloid-based genetically driven mouse models of AD. Together with mixed pathology in the vast majority of the patients with late-onset dementia, these findings strongly suggest the existence of common pathogenesis of diverse neurodegenerative disorders. Anti-oxidative strategy such as DJ-1 modulation is one of the major candidates to address the common pathogenesis and should be assembled among multimodal or combinatory interventions against neurodegenerative disorders.