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Mutations in leucine rich repeat kinase 2 (LRRK2) are responsible for autosomal dominant Parkinson’s disease (PD). G2019S remains the most common mutation, but is rare in Asia, while LRRK2 Asian-specific variants are associated with increased risk of PD.1 LRRK2 interacts with human peroxiredoxin 3 (PRDX3),2 a mitochondrial member of the antioxidant family of thioredoxin (Trx) peroxidases, increasing its inhibition and leading to mitochondrial dysfunction and oxidative damage.2 Mutations in LRRK2 reduce peroxidase activity and increase neuronal cell death.2 Serum PRDX3 is a surrogate marker of peroxidase activity, with lower levels reflecting lower peroxidase activity, but peripheral PRDX3 levels in PD with and without LRRK2 mutations have not been investigated. We hypothesised that PRDX3 levels may discriminate PD LRRK2 mutation carriers (PD+LRRK2+) from LRRK non-mutation carriers (PD+LRRK2−).
Participants were prospectively recruited from the National Neuroscience Institute, Singapore between November 2014 and October 2019. All patients with PD fulfilled the National Institute of Neurological Disorders and Stroke criteria for the diagnosis of PD. Functional status was determined using the Hoehn and Yahr scoring system, and motor severity was measured using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (UPDRS) Part III Motor component. Global cognition was measure using the Mini–Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) tools. …
ASN and JT are joint first authors.
LCT and EKT are joint senior authors.
Contributors AN and YT contributed equally to this paper. Conception and design: AN, YT and EKT. Acquisition of data: YT, EN, KYT, WLA, LT and EKT. Analysis and interpretation of data: AN and YT. Writing of the first draft: AN and YT. Review and critique: EKT. Reviewed manuscript: all authors.
Funding This study was funded by Singapore’s National Medical Research Council (AN by the Clinician-Scientist New Investigator Grant (CNIG/1165/2017) and Transition Award (MOH-TA18may-0003); EKT and LT by the Parkinson’s disease Translational and Clinical Research flagship grant (TCR12dec010), Open Fund Large Collaborative Grant (MOH-OFLCG18May-0002), and Singapore Translational Research (STaR) Investigator award (NMRC/STaR/014/2013)). Part of the data and biospecimens used in this study were obtained from the MJFF LCC, which is coordinated and funded by the Michael J Fox Foundation for Parkinson’s disease research. For up-to-date information on the LCC study, visit https://www.michaeljfox.org/page.html?lrrk2-cohort-consortium.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.