Therapeutic Role of Protein Tyrosine Phosphatase 1B in Parkinson’s Disease via Antineuroinflammation and Neuroprotection In Vitro and In Vivo

Feng, Chien-Wei; Chen, Nan‐Fu; Chan, Te-Fu; Chen, Wu-Fu

doi:10.1155/2020/8814236

Cited by 9 publications

(9 citation statements)

References 73 publications

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“…8 ). Interestingly, a few studies have shown that PTP1B has a pro-neuroinflammation ability through its enhancement of the release of TNF-α, iNOS, and IL-6 170 , 171 in the brain or GSK3β in PD. 172 Recently, PTP1B was demonstrated to have dual roles in modulating the inflammation response in alcoholic liver injury 173 and non-alcoholic fatty liver disease 174 through its modulation of the inflammatory response.…”

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

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Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage. On the other hand, inflammation can also initiate tissue damage repair and maintain normal tissue function by resolving injury and restoring homeostasis. These opposing functions emphasize the significance of accurate regulation of inflammatory homeostasis to ameliorate inflammation-related diseases. Potential mechanisms involve protein phosphorylation modifications by kinases and phosphatases, which have a crucial role in inflammatory homeostasis. The mechanisms by which many kinases resolve inflammation have been well reviewed, whereas a systematic summary of the functions of protein phosphatases in regulating inflammatory homeostasis is lacking. The molecular knowledge of protein phosphatases, and especially the unique biochemical traits of each family member, will be of critical importance for developing drugs that target phosphatases. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of all protein phosphatases in inflammation-related diseases, as well as their potential inhibitors or activators that can be used in therapeutic interventions in preclinical or clinical trials. We provide an integrated perspective on the current understanding of all the protein phosphatases associated with inflammation-related diseases, with the aim of facilitating the development of drugs that target protein phosphatases for the treatment of inflammation-related diseases.

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Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

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“…Therefore, blocking this enzyme is an attractive strategy to treat both diabetes and obesity, which represents an advantage over existing therapies to date. Furthermore, PTP1B has gained much attention in recent years since it is involved in other diseases such as Alzheimer’s [ 5 ], Parkinson’s disease [ 6 , 7 ], cardiovascular disorders [ 8 , 9 , 10 , 11 ], and malignant tumors [ 12 , 13 , 14 , 15 , 16 ]. This makes the development of PTP1B inhibitors even more interesting.…”

Section: Introductionmentioning

confidence: 99%

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

et al. 2021

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Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triterpenoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole- and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 µM. The trifluoromethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 µM) than that of positive controls ursolic acid (IC50 = 5.6 µM), claramine (IC50 = 13.7 µM) and suramin (IC50 = 4.1 µM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.

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“…Several lines of evidence have indicated that NOS-II regulates CXC chemokine production and has a regulatory effect on neutrophil accumulation in various acute inflammations [57][58][59][60]. Moreover, IFN-γ can enhance NOS-II expression in various cells [61][62][63][64]. We found that the expression of Cxcl1, Cxcl2, and Ifng was significantly enhanced in the liver after the APAP challenge.…”

Section: Discussionmentioning

confidence: 57%

Essential Involvement of Neutrophil Elastase in Acute Acetaminophen Hepatotoxicity Using BALB/c Mice

Ishida

Zhang

Kuninaka

et al. 2023

IJMS

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Intense neutrophil infiltration into the liver is a characteristic of acetaminophen-induced acute liver injury. Neutrophil elastase is released by neutrophils during inflammation. To elucidate the involvement of neutrophil elastase in acetaminophen-induced liver injury, we investigated the efficacy of a potent and specific neutrophil elastase inhibitor, sivelestat, in mice with acetaminophen-induced acute liver injury. Intraperitoneal administration of 750 mg/kg of acetaminophen caused severe liver damage, such as elevated serum transaminase levels, centrilobular hepatic necrosis, and neutrophil infiltration, with approximately 50% mortality in BALB/c mice within 48 h of administration. However, in mice treated with sivelestat 30 min after the acetaminophen challenge, all mice survived, with reduced serum transaminase elevation and diminished hepatic necrosis. In addition, mice treated with sivelestat had reduced NOS-II expression and hepatic neutrophil infiltration after the acetaminophen challenge. Furthermore, treatment with sivelestat at 3 h after the acetaminophen challenge significantly improved survival. These findings indicate a new clinical application for sivelestat in the treatment of acetaminophen-induced liver failure through mechanisms involving the regulation of neutrophil migration and NO production.

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Therapeutic Role of Protein Tyrosine Phosphatase 1B in Parkinson’s Disease via Antineuroinflammation and Neuroprotection In Vitro and In Vivo

Cited by 9 publications

References 73 publications

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Indole- and Pyrazole-Glycyrrhetinic Acid Derivatives as PTP1B Inhibitors: Synthesis, In Vitro and In Silico Studies

Essential Involvement of Neutrophil Elastase in Acute Acetaminophen Hepatotoxicity Using BALB/c Mice

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