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LRRK2 Parkinsonism: Does the Response to Gut Bacteria Mitigate the Neurological Picture?

Menozzi, E; Macnaughtan, J; Schapira, AHV; (2020) LRRK2 Parkinsonism: Does the Response to Gut Bacteria Mitigate the Neurological Picture? Movement Disorders 10.1002/mds.28347. (In press).

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Abstract

Mutations in the leucine‐rich repeat kinase 2 (LRRK2, OMIM 609007) gene were first associated with autosomal‐dominant forms of Parkinson disease (PD) more than 15 years ago. Since then, at least 7 missense mutations (N1437H, R1441C/G/H, Y1699C, G2019S, I2020T) have been confirmed as pathogenic for PD, and genome‐wide association studies have consistently confirmed an association between PD risk and polymorphism in LRRK2 loci. Pathogenic mutations in LRRK2 are widely regarded as the most common cause of autosomal dominantly inherited PD (PARK‐LRRK2, OMIM 607060),1 with variable age‐dependent penetrance (30%–74%).2 Here, we propose why PARK‐LRRK2 should be considered a distinct, more benign form of PD. Further, we outline the crucial role of LRRK2 protein in modulating immune and infection responses, especially within the gut, and critically discuss how this might impact PARK‐LRRK2 onset, progression, and pathogenesis compared with PD.

Type: Article
Title: LRRK2 Parkinsonism: Does the Response to Gut Bacteria Mitigate the Neurological Picture?
Location: United States
DOI: 10.1002/mds.28347
Publisher version: http://dx.doi.org/10.1002/mds.28347
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: LRRK2, Parkinson, gut immunity, gut-brain axis, microbiome
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10113941
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