DJ-1 function and oxidative stress

Cookson, Mark

Abstract

We have been interested in the relationship between oxidative stress and DJ-1, a rare cause of recessive Parkinson's disease, for several years and have focussed the relationship between oxidative stress and mitochondrial localization. In the current period, we have explored the effects of DJ-1 deficiency in the brains of mice and rats. We find that loss of DJ-1 alters cellular signaling pathways that result, at a cellular level, in the accumulation of changes in metabolic enyzmes. We are currently exploring the mechanism(s) by which this occurs and determining the output of these changes on neurons and glia in the brain.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute on Aging (NIA)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAG000953-15
• Application #: 9351991
• Support Year: 15
• Fiscal Year: 2016

Institution

• Name: Aging

Publications

Hauser, David N; Mamais, Adamantios; Conti, Melissa M et al. (2017) Hexokinases link DJ-1 to the PINK1/parkin pathway. Mol Neurodegener 12:70

Hauser, David N; Primiani, Christopher T; Cookson, Mark R (2017) The Effects of Variants in the Parkin, PINK1, and DJ-1 Genes along with Evidence for their Pathogenicity. Curr Protein Pept Sci 18:702-714

Cookson, Mark R (2017) RNA-binding proteins implicated in neurodegenerative diseases. Wiley Interdiscip Rev RNA 8:

Hauser, David N; Dillman, Allissa A; Ding, Jinhui et al. (2014) Post-translational decrease in respiratory chain proteins in the Polg mutator mouse brain. PLoS One 9:e94646

Prahlad, Janani; Hauser, David N; Milkovic, Nicole M et al. (2014) Use of cysteine-reactive cross-linkers to probe conformational flexibility of human DJ-1 demonstrates that Glu18 mutations are dimers. J Neurochem 130:839-53

Cookson, Mark R (2012) Parkinsonism due to mutations in PINK1, parkin, and DJ-1 and oxidative stress and mitochondrial pathways. Cold Spring Harb Perspect Med 2:a009415

Hauser, David N; Cookson, Mark R (2011) Astrocytes in Parkinson's disease and DJ-1. J Neurochem 117:357-8

Thomas, Kelly Jean; McCoy, Melissa K; Blackinton, Jeff et al. (2011) DJ-1 acts in parallel to the PINK1/parkin pathway to control mitochondrial function and autophagy. Hum Mol Genet 20:40-50

McCoy, Melissa K; Cookson, Mark R (2011) DJ-1 regulation of mitochondrial function and autophagy through oxidative stress. Autophagy 7:531-2

Cookson, Mark R (2010) Unravelling the role of defective genes. Prog Brain Res 183:43-57