LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson’s Disease, Where Do We Stand?
Identifieur interne : 001863 ( Ncbi/Curation ); précédent : 001862; suivant : 001864LRRK2 Kinase Inhibition as a Therapeutic Strategy for Parkinson’s Disease, Where Do We Stand?
Auteurs : Jean-Marc Taymans [France] ; Elisa Greggio [Italie]Source :
- Current Neuropharmacology [ 1570-159X ] ; 2016.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (therapeutic use), Drug Evaluation, Preclinical, Enzyme Inhibitors (therapeutic use), Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (genetics), Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (metabolism), Parkinson Disease (genetics), Parkinson Disease (therapy).
- MESH :
- chemical , genetics : Leucine-Rich Repeat Serine-Threonine Protein Kinase-2.
- chemical , metabolism : Leucine-Rich Repeat Serine-Threonine Protein Kinase-2.
- chemical , therapeutic use : Antiparkinson Agents, Enzyme Inhibitors.
- genetics : Parkinson Disease.
- therapy : Parkinson Disease.
- Animals, Drug Evaluation, Preclinical, Humans.
Abstract
One of the most promising therapeutic targets for potential diseasemodifying treatment of Parkinson’s disease (PD) is leucine-rich repeat kinase 2 (LRRK2). Specifically, targeting LRRK2’s kinase function has generated a lot of interest from both industry and academia. This work has yielded several published studies showing the feasibility of developing potent, selective and brain permeable LRRK2 kinase inhibitors. The availability of these experimental drugs is contributing to filling in the gaps in our knowledge on the safety and efficacy of LRRK2 kinase inhibition. Recent studies of LRRK2 kinase inhibition in preclinical models point to potential undesired effects in peripheral tissues such as lung and kidney. Also, while strategies are now emerging to measure target engagement of LRRK2 inhibitors, there remains an important need to expand efficacy studies in preclinical models of progressive PD. Future work in the LRRK2 inhibition field must therefore be directed towards developing molecules and treatment regimens which demonstrate efficacy in mammalian models of disease in conditions where safety liabilities are reduced to a minimum.
Url:
DOI: 10.2174/1570159X13666151030102847
PubMed: 26517051
PubMed Central: 4857626
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PMC:4857626Le document en format XML
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<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (genetics)</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 (metabolism)</term>
<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (therapy)</term>
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<term>Enzyme Inhibitors</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term>
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<front><div type="abstract" xml:lang="en"><p>One of the most promising therapeutic targets for potential diseasemodifying
treatment of Parkinson’s disease (PD) is leucine-rich repeat kinase 2 (LRRK2).
Specifically, targeting LRRK2’s kinase function has generated a lot of interest from
both industry and academia. This work has yielded several published studies showing
the feasibility of developing potent, selective and brain permeable LRRK2 kinase
inhibitors. The availability of these experimental drugs is contributing to filling in the
gaps in our knowledge on the safety and efficacy of LRRK2 kinase inhibition. Recent studies of LRRK2 kinase inhibition
in preclinical models point to potential undesired effects in peripheral tissues such as lung and kidney. Also, while
strategies are now emerging to measure target engagement of LRRK2 inhibitors, there remains an important need to
expand efficacy studies in preclinical models of progressive PD. Future work in the LRRK2 inhibition field must
therefore be directed towards developing molecules and treatment regimens which demonstrate efficacy in mammalian
models of disease in conditions where safety liabilities are reduced to a minimum.</p>
</div>
</front>
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