Abstract
Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. However, the currently available treatments could only relieve symptoms. Novel therapeutic targets are urgently needed. Several previous studies mentioned that protein tyrosine phosphatase 1B (PTP1B) acted as a negative regulator of the insulin signal pathway and played a significant role in the inflammation process. However, few studies have investigated the role of PTP1B in the central nervous system. Our study showed that suramin, an inhibitor of PTP1B, could improve neuronal damage. It could significantly attenuate the interferon-gamma-induced upregulation of proinflammatory cytokines, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). It enhanced M2 type microglia markers, such as arginase-1 and Ym-1 in BV2 murine microglial cells. PTP1B inhibition also reversed 6-hydroxydopamine- (6-OHDA-) induced downregulation of phospho-cAMP response element-binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) in SH-SY5Y cells. Besides, we knocked down and overexpressed PTP1B in the SH-SY5Y cells to confirm its role in neuroprotection. We also verified the effect of suramin in the zebrafish PD model. Treatment with suramin could significantly reverse 6-OHDA-induced locomotor deficits and improved tyrosine hydroxylase (TH) via attenuating endoplasmic reticulum (ER) stress biomarkers. These results support that PTP1B could potentially regulate PD via antineuroinflammation and antiapoptotic pathways.
Highlights
Over the last few decades, the NIH reported that approximately 50,000 patients were diagnosed with Parkinson’s disease (PD) every year in America
We examined the anti-inflammatory activity in BV2 murine microglial cells using western blotting
Our data demonstrated that IFN-c significantly increased inducible nitric oxide synthase (iNOS) and COX2 protein expression in BV2 murine microglial cells and 0.1, 1, and 10 μM suramin significantly inhibited iNOS, COX-2, and NF-κB (p65) protein expression (Figure 1(a))
Summary
Over the last few decades, the NIH reported that approximately 50,000 patients were diagnosed with Parkinson’s disease (PD) every year in America. The global PD pharmaceutical market was estimated at 4.02 billion in 2016 which will increase to 6.48 billion USD in 2024 with a compound annual growth rate (CAGR) of 6.15%. About 1 million patients suffer from PD in the US [1, 2]. The current PD treatments can only relieve the clinical symptoms but cannot delay disease progression. No cure is currently available, and there is a tremendous demand for effective agents or strategies for the prevention or attenuation of PD progression. Several therapeutic targets have been investigated to help PD patients
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