Targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of Parkinson's disease
Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine kinase involved in multiple cellular processes and signaling pathways. LRRK2 mutations are associated with autosomal-inherited Parkinson's disease (PD), and evidence suggests that LRRK2 pathogenic variants generally increase kinase activity. Therefore, inhibition of LRRK2 kinase function is a promising therapeutic strategy for PD treatment. The search for drug-like molecules capable of reducing LRRK2 kinase activity in PD led to the design of selective LRRK2 inhibitors predicted to be within the CNS drug-like space. This review highlights the journey that translates chemical tools for interrogating the role of LRRK2 in PD into promising drug candidates, addressing the challenges in discovering selective and brain-penetrant LRRK2 modulators and exploring the structure-activity relationship of distinct LRRK2 inhibitors.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
|---|---|
| Enthalten in: |
Future medicinal chemistry - 11(2019), 15 vom: 15. Aug., Seite 1953-1977 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Domingos, Sofia [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 20.05.2020 Date Revised 20.05.2020 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.4155/fmc-2018-0484 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM301260621 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM301260621 | ||
| 003 | DE-627 | ||
| 005 | 20231225104247.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.4155/fmc-2018-0484 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1004.xml |
| 035 | |a (DE-627)NLM301260621 | ||
| 035 | |a (NLM)31517532 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Domingos, Sofia |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Targeting leucine-rich repeat kinase 2 (LRRK2) for the treatment of Parkinson's disease |
| 264 | 1 | |c 2019 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.05.2020 | ||
| 500 | |a Date Revised 20.05.2020 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Leucine-rich repeat kinase 2 (LRRK2) is a serine-threonine kinase involved in multiple cellular processes and signaling pathways. LRRK2 mutations are associated with autosomal-inherited Parkinson's disease (PD), and evidence suggests that LRRK2 pathogenic variants generally increase kinase activity. Therefore, inhibition of LRRK2 kinase function is a promising therapeutic strategy for PD treatment. The search for drug-like molecules capable of reducing LRRK2 kinase activity in PD led to the design of selective LRRK2 inhibitors predicted to be within the CNS drug-like space. This review highlights the journey that translates chemical tools for interrogating the role of LRRK2 in PD into promising drug candidates, addressing the challenges in discovering selective and brain-penetrant LRRK2 modulators and exploring the structure-activity relationship of distinct LRRK2 inhibitors | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 4 | |a LRRK2 | |
| 650 | 4 | |a LRRK2 G2019S mutation | |
| 650 | 4 | |a LRRK2 inhibitors | |
| 650 | 4 | |a Parkinson's disease | |
| 650 | 4 | |a blood–brain barrier | |
| 650 | 4 | |a kinase inhibitors | |
| 650 | 4 | |a kinase selectivity | |
| 650 | 4 | |a neurodegeneration | |
| 650 | 4 | |a serine-threonine kinase | |
| 650 | 4 | |a small molecule inhibitors | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Protein Kinase Inhibitors |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Small Molecule Libraries |2 NLM | |
| 650 | 7 | |a Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Duarte, Teresa |e verfasserin |4 aut | |
| 700 | 1 | |a Saraiva, Lucília |e verfasserin |4 aut | |
| 700 | 1 | |a Guedes, Rita C |e verfasserin |4 aut | |
| 700 | 1 | |a Moreira, Rui |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Future medicinal chemistry |d 2009 |g 11(2019), 15 vom: 15. Aug., Seite 1953-1977 |w (DE-627)NLM194822109 |x 1756-8927 |7 nnns |
| 773 | 1 | 8 | |g volume:11 |g year:2019 |g number:15 |g day:15 |g month:08 |g pages:1953-1977 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.4155/fmc-2018-0484 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 11 |j 2019 |e 15 |b 15 |c 08 |h 1953-1977 | ||