Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To examine whether 14-3-3 phosphorylation is altered in Parkinson’s disease and other neurodegenerative disorders.
Background: 14-3-3 proteins are a highly conserved family of proteins that play an important role in cell survival. 14-3-3s interact with key players implicated in Parkinson’s disease (PD), including alpha-synuclein and LRRK2. We have shown that overexpression of certain 14-3-3 isoforms are protective in neurotoxin, alpha-synuclein, and LRRK2 models of PD, while inhibition leads to increased toxicity. Phosphorylation of 14-3-3s is a key mechanism for regulating 14-3-3 function. We recently observed that increased 14-3-3 phosphorylation is increased in several PD models and that phosphorylation of 14-3-3s reduces their neuroprotective effects.
Methods: In the present study we investigated 14-3-3 phosphorylation at three conserved sites, serine 58 (S58), serine 185 (S185) and serine 232 (S232), in postmortem temporal cortical samples from PD, Alzheimer’s disease (AD), Lewy body dementia (DLB), progressive supranuclear palsy (PSP), and control subjects. Lysates from temporal cortices were fractionated into Triton X-100 soluble and insoluble fractions, and examined for 14-3-3 phosphorylation and total 14-3-3 levels by Western blotting.
Results: S58 phosphorylation was largely unchanged. S185 phosphorylation was elevated by 44% in Triton-soluble lysates in DLB. S232 phosphorylation was altered in several disorders, with a reduction in S232 phosphorylation in the soluble fraction by 44% and 34% in AD and DLB, respectively, and an increase in S232 phosphorylation by 37%, 42%, and 42% in PD, AD, and DLB, respectively, in the insoluble fraction. No phosphorylation changes were noted in PSP. Total 14-3-3 levels were dramatically reduced in the soluble fraction by 34% in AD and 37% in DLB.
Conclusions: Our data show that 14-3-3 phosphorylation is a marker of neurodegeneration, but these neurodegenerative disorders differ in which phosphorylation sites are altered. These data point to the potential role of 14-3-3 phosphorylation in the pathophysiology of neurodegeneration and suggest that 14-3-3 phosphorylation may serve as a potential biomarker for neurodegeneration.
To cite this abstract in AMA style:
T. Yacoubian, X. Chi, G. Cutter, M. McFerrin. Alterations in 14-3-3 protein phosphorylation as a biomarker for neurodegeneration [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/alterations-in-14-3-3-protein-phosphorylation-as-a-biomarker-for-neurodegeneration/. Accessed May 19, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/alterations-in-14-3-3-protein-phosphorylation-as-a-biomarker-for-neurodegeneration/