The α7 nAChR allosteric modulator PNU-120596 amends neuroinflammatory and motor consequences of parkinsonism in rats: Role of JAK2/NF-κB/GSk3β/ TNF-α pathway

Gowayed, Mennatallah A.; El-Sayed, Norhan S; Matar, Noura A; Afify, Elham A.; El-Ganainy, Samar O.

doi:10.1016/j.biopha.2022.112776

Cited by 4 publications

(1 citation statement)

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“…139 The rapid binding kinetics of PNU-120596 indicated that p38MAPK binding of PNU-120596 was more likely to be DFG-in binding. In the study of improving neuroinflammation and movement in rats with PD, 140 PNU-120596 inhibited striatal neuroinflammation, which was manifested as the inhibition of JAK2/NF-κB/GSk3β expression, and the expression level of TNF-α protein in nigrostriatal tissue was decreased, reflecting the anti-inflammatory ability of this substance. However, at high concentrations, PNU-120596 showed a relatively low inhibitory effect on p38MAPK.…”

Section: Pyrazole Derivativesmentioning

confidence: 99%

p38 mitogen‐activated protein kinase: Functions and targeted therapy in diseases

Zheng,

Li,

Wang

et al. 2023

MedComm – Oncology

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P38 mitogen‐activated protein kinase (p38MAPK) is a multifunctional protein kinase that plays an important role in human normal physiological activities and a variety of major diseases, and its signaling pathway affects a variety of regulatory factors in vivo, which is related to cell cycle, survival, metabolism, and differentiation. The four subtypes of p38MAPK have significant differences in their distribution, content, and effects in the body. The inhibitors of the four subtypes play potential roles in regulating cancer, neurodegenerative diseases, inflammation, and cardiovascular diseases, making it an attractive target for drug development. So far, an increasing number of p38MAPK inhibitors have been developed for targeted therapy in diseases, among which some representative compounds have entered clinical trials. Therefore, this review aims to provide a summary of the structural characteristics, signaling pathways of P38MAPK and the relationship between p38MAPK and disease, along with an overview of the binding modes and structure–activity relationships of small molecule inhibitors targeting four p38MAPK subtypes, and summarizes the challenges about the development of p38MAPK inhibitors, hoping to provide a valuable reference for the development and application of novel inhibitors.

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Section: Pyrazole Derivativesmentioning

confidence: 99%