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)
The derangement of tyrosine hydroxylase (TH) activity reduces dopamine synthesis and is implicated in the pathogenesis of Parkinson's disease. However, the extracellular modulator and intracellular regulatory mechanisms of TH have yet to be identified. Recently,
high-mobility group box 1
(
HMGB1
) was reported to be actively secreted from glial cells and is regarded as a mediator of dopaminergic neuronal loss. However, the mechanism for how
HMGB1
affects TH expression, particularly through the receptor for advanced glycation endproducts (RAGE), has not yet been investigated. We found that recombinant
HMGB1
(rHMGB1) upregulates TH mRNA expression via simultaneous activation of JNK phosphorylation, and this induction of TH expression is blocked by inhibitors of RAGE and JNK. To investigate how TH expression levels change through the
HMGB1
-RAGE axis as a result of
MPP
+
toxicity, we co-treated SN4741 dopaminergic cells with
MPP
+
and rHMGB1. rHMGB1 blocked the reduction of TH mRNA following
MPP
+
treatment without altering cell survival rates. Our results suggest that
HMGB1
upregulates TH expression to maintain dopaminergic neuronal function via activating RAGE, which is dependent on JNK phosphorylation.
...
PMID:Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation. 2888 39
