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Exosome markers of LRRK2 kinase inhibition.

Publication ,  Journal Article
Wang, S; Kelly, K; Brotchie, JM; Koprich, JB; West, AB
Published in: NPJ Parkinsons Dis
November 13, 2020

Hyper-activated LRRK2 is linked to Parkinson's disease susceptibility and progression. Quantitative measures of LRRK2 inhibition, especially in the brain, maybe critical in the development of successful LRRK2-targeting therapeutics. In this study, two different brain-penetrant and selective LRRK2 small-molecule kinase inhibitors (PFE-360 and MLi2) were orally administered to groups of cynomolgus macaques. Proposed pharmacodynamic markers in exosomes from urine and cerebrospinal fluid (CSF) were compared to established markers in peripheral blood mononuclear cells (PBMCs). LRRK2 kinase inhibition led to reductions in exosome-LRRK2 protein and the LRRK2-substrate pT73-Rab10 in urine, as well as reduced exosome-LRRK2 and autophosphorylated pS1292-LRRK2 protein in CSF. We propose orthogonal markers for LRRK2 inhibition in urine and CSF can be used in combination with blood markers to non-invasively monitor the potency of LRRK2-targeting therapeutics.

Duke Scholars

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Published In

NPJ Parkinsons Dis

DOI

ISSN

2373-8057

Publication Date

November 13, 2020

Volume

6

Issue

1

Start / End Page

32

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 5202 Biological psychology
  • 3209 Neurosciences
 

Citation

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Wang, S., Kelly, K., Brotchie, J. M., Koprich, J. B., & West, A. B. (2020). Exosome markers of LRRK2 kinase inhibition. NPJ Parkinsons Dis, 6(1), 32. https://doi.org/10.1038/s41531-020-00138-7
Wang, Shijie, Kaela Kelly, Jonathan M. Brotchie, James B. Koprich, and Andrew B. West. “Exosome markers of LRRK2 kinase inhibition.NPJ Parkinsons Dis 6, no. 1 (November 13, 2020): 32. https://doi.org/10.1038/s41531-020-00138-7.
Wang S, Kelly K, Brotchie JM, Koprich JB, West AB. Exosome markers of LRRK2 kinase inhibition. NPJ Parkinsons Dis. 2020 Nov 13;6(1):32.
Wang, Shijie, et al. “Exosome markers of LRRK2 kinase inhibition.NPJ Parkinsons Dis, vol. 6, no. 1, Nov. 2020, p. 32. Pubmed, doi:10.1038/s41531-020-00138-7.
Wang S, Kelly K, Brotchie JM, Koprich JB, West AB. Exosome markers of LRRK2 kinase inhibition. NPJ Parkinsons Dis. 2020 Nov 13;6(1):32.

Published In

NPJ Parkinsons Dis

DOI

ISSN

2373-8057

Publication Date

November 13, 2020

Volume

6

Issue

1

Start / End Page

32

Location

United States

Related Subject Headings

  • 5204 Cognitive and computational psychology
  • 5202 Biological psychology
  • 3209 Neurosciences