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DIGITAL.CSIC
Article . 2019 . Peer-reviewed
Data sources: DIGITAL.CSIC
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Journal of Medicinal Chemistry
Article . 2019 . Peer-reviewed
License: STM Policy #29
Data sources: Crossref
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Benzothiazole-Based LRRK2 Inhibitors as Wnt Enhancers and Promoters of Oligodendrocytic Fate

Authors: Josefa Zaldivar-Diez; Lingling Li; Ana M. Garcia; Wen-Ning Zhao; Cristina Medina-Menendez; Stephen. J. Haggarty; Carmen Gil; +2 Authors

Benzothiazole-Based LRRK2 Inhibitors as Wnt Enhancers and Promoters of Oligodendrocytic Fate

Abstract

Leucine rich repeat kinase 2 (LRRK2) is an enigmatic enzyme and a relevant target for Parkinson's disease (PD). However, despite the significant amount of research done in the past decade, the precise function of LRRK2 remains largely unknown. Moreover, the therapeutic potential of its inhibitors is in its infancy with the first clinical trial having just started. In the present work, the molecular mechanism of LRRK2 in the control of neurogenesis or gliogenesis was investigated. We designed and synthesized novel benzothiazole-based LRRK2 inhibitors and showed that they can modulate the Wnt/β-catenin signaling pathway. Furthermore, compounds 5 and 14 were able to promote neural progenitors proliferation and drive their differentiation toward neuronal and oligodendrocytic cell fates. These results suggest potential new avenues for the application of LRRK2 inhibitors in demyelinating diseases in which oligodendrocyte cell-death is one of the pathological features.

Country
Spain
Keywords

Male, Neurogenesis, Parkinson Disease, Oligodendrocyte differentiation, Adult neurogenesis, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Mice, Inbred C57BL, Molecular Docking Simulation, Mice, Oligodendroglia, LRRK2 inhibitors, Wnt enhancers, Animals, Humans, Female, Benzothiazoles, Protein Kinase Inhibitors, Wnt Signaling Pathway, Cells, Cultured

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
views
OpenAIRE UsageCountsViews provided by UsageCounts
downloads
OpenAIRE UsageCountsDownloads provided by UsageCounts
16
Top 10%
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86
306
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bronze