Tyrosine Metabolism Pathway Is Downregulated in Dopaminergic Neurons with LRRK2 Overexpression in

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Nov 14

PMID 37958569

Authors

Jack Cheng

Bor-Tsang Wu

Hsin-Ping Liu

Wei-Yong Lin

Affiliations

Soon will be listed here.

Abstract

LRRK2 mutations are the leading cause of familial Parkinson's disease (PD) and are a significant risk factor for idiopathic PD cases. However, the molecular mechanisms underlying the degeneration of dopaminergic (DA) neurons in LRRK2 PD patients remain unclear. To determine the translatomic impact of LRRK2 expression in DA neurons, we employed gene set enrichment analysis (GSEA) to analyze a translating ribosome affinity purification (TRAP) RNA-seq dataset from a DA-neuron-specific-expressing model. We found that the tyrosine metabolism pathway, including tyrosine hydroxylase (TH), is downregulated in DA neurons with LRRK2 overexpression; in contrast, the Hippo signaling pathway is downregulated in the G2019S mutant compared to wild-type LRRK2 in the DA neurons. These results imply that the downregulation of tyrosine metabolism occurs before pronounced DA neuron loss and that LRRK2 may downregulate the tyrosine metabolism in a DA-neuron-loss-independent way.

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