title: LRRK2 detection in human biofluids: potential use as a Parkinson's disease biomarker?
abstract: Leucine-rich repeat kinase 2 (LRRK2) is a complex signalling protein that is a key therapeutic target, particularly in Parkinson's disease (PD). In addition, there is now evidence showing that LRRK2 expression and phosphorylation levels have potential as markers of disease or target engagement. Indeed, reports show increases in LRRK2 protein levels in the prefrontal cortex of PD patients relative to controls, suggesting that increase in total LRRK2 protein expression is correlated with disease progression. LRRK2 phosphorylation levels are reduced in experimental systems for most disease mutants, and LRRK2 is also rapidly dephosphorylated upon LRRK2 inhibitor treatment, considered potential therapeutics. Recently, the presence of LRRK2 was confirmed in exosomes from human biofluids, including urine and cerebrospinal fluid. Moreover, phosphorylation of LRRK2 at phosphosites S910, S935, S955 and S973, as well as at the autophosphoryation site S1292, was found in urinary exosomes. In this review, we summarize knowledge on detection of LRRK2 in human biofluids and the relevance of these findings for the development of PD-related biomarkers.
authors.affiliation: Université de Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France jean-marc.taymans@inserm.fr marie-christine.chartier-harlin@inserm.fr.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Taymans
authors.affiliation: Université de Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France.
authors.forename: Eugénie
authors.initials: E
authors.lastname: Mutez
authors.affiliation: Université de Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Drouyer
authors.affiliation: Université de Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France.
authors.forename: William
authors.initials: W
authors.lastname: Sibran
authors.affiliation: Université de Lille, Inserm, CHU Lille, UMR-S1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000 Lille, France jean-marc.taymans@inserm.fr marie-christine.chartier-harlin@inserm.fr.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chartier-Harlin
mesh_terms: D000595:Amino Acid Sequence; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid* / Q000652:urine; D055354:Exosomes / Q000201:enzymology; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation; D017397:Prefrontal Cortex / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012694:Serine; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
keywords: LRRK2; Parkinson's disease; biomarkers