Vitamin B
Allosteric Regulation
Animals
Caenorhabditis elegans
Cobamides
/ pharmacology
Disease Models, Animal
Drosophila melanogaster
Drug Repositioning
HEK293 Cells
Humans
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
/ metabolism
Mice
Mice, Inbred C57BL
Neuroprotective Agents
/ pharmacology
Parkinson Disease
/ drug therapy
Rats
Vitamin B 12
/ analogs & derivatives
Vitamin B Complex
/ pharmacology
Journal
Cell research
ISSN: 1748-7838
Titre abrégé: Cell Res
Pays: England
ID NLM: 9425763
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
31
08
2018
accepted:
09
02
2019
pubmed:
13
3
2019
medline:
10
9
2020
entrez:
13
3
2019
Statut:
ppublish
Résumé
Missense mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) cause the majority of familial and some sporadic forms of Parkinson's disease (PD). The hyperactivity of LRRK2 kinase induced by the pathogenic mutations underlies neurotoxicity, promoting the development of LRRK2 kinase inhibitors as therapeutics. Many potent and specific small-molecule LRRK2 inhibitors have been reported with promise. However, nearly all inhibitors are ATP competitive-some with unwanted side effects and unclear clinical outcome-alternative types of LRRK2 inhibitors are lacking. Herein we identify 5'-deoxyadenosylcobalamin (AdoCbl), a physiological form of the essential micronutrient vitamin B
Identifiants
pubmed: 30858560
doi: 10.1038/s41422-019-0153-8
pii: 10.1038/s41422-019-0153-8
pmc: PMC6462009
doi:
Substances chimiques
Cobamides
0
Neuroprotective Agents
0
Vitamin B Complex
12001-76-2
LRRK2 protein, human
EC 2.7.11.1
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
EC 2.7.11.1
cobamamide
F0R1QK73KB
Vitamin B 12
P6YC3EG204
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
313-329Subventions
Organisme : NINDS NIH HHS
ID : P50 NS094733
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM115844
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS060809
Pays : United States
Organisme : Parkinson's UK
ID : K-1704
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 097829/Z/11/A
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R21 NS073170
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS097530
Pays : United States
Organisme : Parkinson's UK
ID : K-1007
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
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