Elevated Serum SIRT 2 May Differentiate Parkinson's Disease From Atypical Parkinsonian Syndromes.

Teena Bajaj,Sadanand Dwivedi,A B Dey,Sharmistha Dey,Amrendra Pratap Singh,Madhuri Behari,Vishwajeet Singh,G Ramana

doi:10.3389/fnmol.2019.00129

Teena Bajaj, Sadanand Dwivedi + Show 6 more

Open Access

https://doi.org/10.3389/fnmol.2019.00129

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Abstract

Atypical Parkinson syndromes (APSs) often have symptoms that overlap with those of Parkinson’s disease (PD), especially early in the disease, making these disorders difficult to diagnose. Previous studies have demonstrated an association of oligomeric α-synuclein (α-Syn), a key element in the pathogenesis of PD, with Sirtuin (SIRT)2 proteins for modulating PD. We aimed to evaluate SIRT protein expression in serum of PD patients and compare it with APSs and normal elderly control (GC) and to correlate this with α-Syn. SIRT protein expression was evaluated in sera of 68 PD; 34 APS and 68 GC without any neuro-psychiatric illness as controls by surface plasmon resonance (SPR). SIRT2 expression was correlated with α-Syn in PD and GC. Significant (p < 0.0001) differences were observed between serum SIRT2 concentration in PD and APS and GC as well as between APS and GC. Receiver operating characteristic (ROC) analysis revealed the strong cut-off value to differentiate PD from APS and GC and also APS from GC. Significant correlation was observed among SIRT2 levels in early PD patients with Unified Parkinson’s Disease Rating Scale (UPDRS), Hoehn & Yahr (H & Y) and increased duration of disease. In addition, a strong positive correlation of SIRT2 with α-Syn (p < 0.0001) was observed. However, no such difference was detected for serum SIRT1 in cases of PD and APS or for GC. The present study is the first to report elevated serum SIRT2 in PD. The study also provided a simple test to distinguish PD from APS and may have translational utility for diagnosis.

Highlights

Parkinson’s disease (PD) is a common movement disorder of the aging population
This study evaluates the level of SIRT1 and SIRT2 protein expression in the serum of PD patients and compares it with Atypical Parkinson syndromes (APSs) and normal elderly controls (GC) in addition to showing the correlation with serum α-Syn levels
SIRT1 and SIRT2 were estimated for the first time in the serum of PD patients and compared with APSs and GCs

Summary

Introduction

Parkinson’s disease (PD) is a common movement disorder of the aging population. It is the second most common neurodegenerative disorder after Alzheimer’s disease. It affects 1–2 per 1,000 of the population and its prevalence increases with age to affect 1% of the population above 60 years of age (Tysnes and Storstein, 2017). The pathological changes in PD are well established as being the loss of dopaminergic neurons in the substantia nigra and the presence of cytoplasmic inclusions of Lewy bodies (LBs). LBs primarily consist of α-synuclein protein (α-Syn). Α-Syn is primarily expressed by neurons and constitutively released into the extracellular space (Stefanis, 2012). LBs primarily consist of α-synuclein protein (α-Syn). α-Syn is primarily expressed by neurons and constitutively released into the extracellular space (Stefanis, 2012).

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