Journal of Alzheimer’s Disease 55 (2017) 73–75 DOI 10.3233/JAD-160878 IOS Press 73 Commentary Modulation of Parkinson’s Disease Associated Protein Rescues Alzheimer’s Disease Degeneration Akihiko Nunomura a,* , Xiongwei Zhu b and George Perry c a Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi, Japan b Department of Pathology, Case Western Reserve University, Cleveland, OH, USA c UTSA Neurosciences Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA Handling Editor: Jes ´ us ´ Avila Accepted 19 September 2016 Abstract. 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 -synuclein but also insoluble A 42 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. Keywords: -synuclein, Alzheimer’s disease, amyloid-, DJ-1, oxidative stress, Parkinson’s disease Mutations in DJ-1 cause an autosomal recessive, early onset familial form of Parkinson’s disease (PD), PARK7 [1]. DJ-1 plays roles in reducing oxidative stress (OS) and transcriptional regulation [2–5], * Correspondence to: Akihiko Nunomura, MD, PhD, Depart- ment of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan. Tel.: +81 55 273 9847; Fax: +81 55 273 6765; E-mail: anunomura@yamanashi.ac.jp. and loss-of-function mutations lead to the charac- teristic selective neurodegeneration of nigrostriatal dopaminergic neurons. Of particular importance, the cytoprotective roles of DJ-1 are not restricted to the process of neurodegeneration in PD, but are more generally involved in diverse neuronal dam- age including stroke and Alzheimer’s disease (AD) [6–9]. DJ-1 expression decreases markers of OS in vivo, where DJ-1 protects through alleviation of ISSN 1387-2877/17/$35.00 © 2017 – IOS Press and the authors. All rights reserved