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Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag
Published on: December 14, 2017
MAPK-pathway activity, Lrrk2 G2019S, and Parkinson's disease
Linda R White1, Mathias Toft, Sylvia N Kvam
1Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway. linda.white@ntnu.no
Journal of Neuroscience Research
|March 28, 2007
Summary
The G2019S mutation in leucine-rich repeat kinase 2 (LRRK2) gene alters mitogen-activated protein kinase (MAPK) signaling. These changes in signaling proteins are detectable in blood, offering potential for early Parkinson's disease detection.
Area of Science:
- Neuroscience
- Genetics
- Cell Biology
Background:
- The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a common cause of autosomal dominant Parkinson's disease (PD).
- Mitogen-activated protein kinase (MAPK) signaling pathways are implicated in cellular function and disease pathogenesis.
- Investigating peripheral tissues may reveal biomarkers for PD, even in preclinical stages.
Purpose of the Study:
- To investigate alterations in MAPK signaling proteins in leukocytes from individuals with LRRK2 G2019S-associated PD.
- To determine if these signaling changes are specific to G2019S-PD or common to idiopathic PD.
- To explore the potential of leukocyte signaling proteins as biomarkers for PD detection and progression.
Main Methods:
- Collected leukocyte extracts from four groups: G2019S-PD patients, healthy LRRK2 mutation carriers, idiopathic PD patients, and healthy controls.
- Compared total protein levels and phosphorylation status of key signaling proteins: Src, HSP27, p38 MAPK, JNK, and ERK.
- Utilized biochemical assays to quantify protein levels and activation states.
Main Results:
- Reduced phosphorylation of Src, HSP27, and JNK was observed in G2019S-PD patients compared to controls.
- Similar reductions in Src and HSP27 phosphorylation were found in healthy mutation carriers and idiopathic PD patients.
- Significant decreases in total Src levels were noted in G2019S-PD patients, healthy carriers, and idiopathic PD patients.
Conclusions:
- Leukocyte MAPK signaling pathways show significant alterations in Parkinson's disease, irrespective of the underlying genetic cause.
- The G2019S LRRK2 mutation profoundly impacts these signaling pathways, with the most pronounced effects seen in G2019S-associated PD.
- Leukocyte signaling changes may serve as preclinical biomarkers for LRRK2-associated PD, aiding in the development of neuroprotective strategies.
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