Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.64 (
MPP
)
1,876
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies have revealed that protein arginine methyltransferases (PRMTs) are responsible for diverse neurodegenerative diseases. However, their pathophysiological role in dopaminergic neuronal death in Parkinson's disease (PD) has not been evaluated. In this study, we demonstrated that 1-Methyl-4-phenylpyridinium iodide (
MPP
+
), rotenone and paraquat, which cause dopaminergic neuronal cell death, increased
PRMT1
expression in dopaminergic cell line. Dopaminergic neuronal cell death was increased by
PRMT1
overexpression.
MPP
+
-induced cell death was attenuated by
PRMT1
knockdown. Poly (ADP-ribose) polymerase-1 (PARP1) expression and activity, poly-ADP-ribosylation (PARylation), were elevated by
MPP
+
. Moreover, we found that
PRMT1
positively regulates nuclear translocation of apoptosis-inducing factor (AIF). Elevated
PRMT1
expression was observed in the substantia nigra pars compacta of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected mice. Furthermore, MPTP-induced dopaminergic neuronal death was reduced in
PRMT1
haploinsufficient (prmt1
+/-
) mice. These data suggest that
PRMT1
is implicated in PARP1/AIF-mediated dopaminergic neuronal cell death, which might be involved in the pathology of PD. Therefore, our results propose
PRMT1
as a new target to develop a potential treatment of PD.
...
PMID:Protein arginine methyltransferase-1 stimulates dopaminergic neuronal cell death in a Parkinson's disease model. 3253 23
