Objective: To probe kinase-phosphatase dysregulation and peripheral biomarker potential in peripheral blood mononuclear cells (PBMCs) via LRRK2 (kinase), PPM1H and PP2A (phosphatases), LC3 (autophagy), and SNCA (synucleinopathy) gene expression.
Background: Disrupted kinase-phosphatase balance may contribute to pathogenic protein phosphorylation in Parkinson’s disease (PD) leading to dopaminergic neurodegeneration. LRRK2 hyperactivity (G2019S variants, Rab phosphorylation) drives pathogenesis, counterbalanced by PPM1H (Rab dephosphorylation) and PP2A (pSer129-α-synuclein dephosphorylation). While LRRK2 mechanisms are established, phosphatase dysregulation in PD remains underexplored particularly in peripheral PBMCs as non-invasive biomarkers.
Method: 25 PD patients and 14 age-matched healthy controls were recruited. Clinical assessments of motor and cognitive functions were conducted using Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA) scale. PBMCs from 8mL venous blood were isolated via density-gradient centrifugation. Total RNA was isolated from the PBMCs using TRIzol method and reverse transcribed using cDNA Synthesis Kit. Relative gene expression levels of PPM1H, PP2Ac, LRRK2, SNCA, PPP2R2B, and LC3 were quantified using qRT-PCR (GAPDH-normalized ΔΔCt). Mann-Whitney U tests compared groups; Spearman correlations examined gene-clinical severity relationships (JASP v0.19).
Results: In PD, PBMCs showed significant downregulation of PPM1H (p=0.038), PP2Ac (p<0.001), LRRK2 (p<0.001), SNCA (p=0.008) and LC3 (p=0.005) compared to healthy controls. However, PPP2R2B (p=0.361) was found unchanged.
Conclusion: In PD PBMCs, PPM1H (Rab-specific phosphatase) and PP2Ac (pSer129-α-synuclein dephosphorylase) downregulation despite preserved PPP2R2B expression coupled with LRRK2 and SNCA suppression demonstrates kinase-phosphatase imbalance favoring aggregation and impaired autophagy. These results establish that peripheral transcripts can act as novel non-invasive biomarkers, supporting phosphatase activation as promising therapeutic strategy over LRRK2 inhibition.
To cite this abstract in AMA style:
E. Basu, R. Banerjee, B. Biswas, S. Mondal, J. Rungta, S. Sengupta, J. Ganguly, D. Dutta, S. Mukherjee, P. Basu, S. Choudhury, H. Kumar. Unraveling Kinase-Phosphatase Dysregulation in Parkinson’s disease Peripheral Blood Mononuclear Cells Through Targeted Transcript Analysis [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/unraveling-kinase-phosphatase-dysregulation-in-parkinsons-disease-peripheral-blood-mononuclear-cells-through-targeted-transcript-analysis/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/unraveling-kinase-phosphatase-dysregulation-in-parkinsons-disease-peripheral-blood-mononuclear-cells-through-targeted-transcript-analysis/