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Parkinson's disease (PD) is a neurodegenerative disorder that results in motor impairment due to dopaminergic neuronal loss. The pathology of PD is closely associated with neuroinflammation, which can be characterized by astrocyte activation. Thus, targeting the inflammatory response in astrocytes might provide a novel therapeutic approach. We conducted a luciferase assay on an in-house chemical library to identify compounds with anti-inflammatory effects capable of reducing MPP+-induced NF-κB activity in astrocytes. Among the compounds identified, EI-16004, a novel 3-benzyl-N-phenyl-1H-pyrazole-5-carboxamides, exhibited a significant anti-inflammatory effect by significantly reducing MPP+-induced astrocyte activation. Biochemical analysis and docking simulation indicated that EI-16004 inhibited the MPP+-induced phosphorylation of p65 by attenuating ERK phosphorylation, and EI-16004 reduced pro-inflammatory cytokine and chemokine levels in astrocytes. In vivo studies on the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in male C57BL/6 mice showed that EI-16004 ameliorated motor impairment and protected against dopaminergic neuronal loss, and EI-16004 effectively mitigated the MPTP-induced astrocyte activation in striatum (STR) and substantia nigra (SN). These results indicate EI-16004 is a potential neuroprotective agent for the prevention and treatment of astrocyte-mediated neuroinflammatory conditions in PD. [ABSTRACT FROM AUTHOR]

A simple and cost-effective electrochemical synthesis of carbon-based nanomaterials for electrochemical biosensor is of great challenge these days. Our study describes a single-step electrochemical deposition strategy to prepare a nanocomposite of electrochemically reduced graphene oxide (ErGO), multi-walled carbon nanotubes (MWCNTs), and polypyrrole (PPy) in an aqueous solution of pH 7.0 for dopamine (DA) detection. The ErGO/MWCNTs/PPy nanocomposites show enhanced electrochemical performance due to the strong π–π* stacking interactions among ErGO, MWCNTs, and PPy. The efficient interaction of the nanocomposites is confirmed by evaluating its physical and electrochemical characteristics using field-emission scanning electron microscopy, Raman spectroscopy, electrochemical impedance spectroscopy, cyclic voltammetry, and amperometry. The deposited nanocomposites are highly stable on the substrates and possess high surface areas, which is vital to improve the sensitivity and selectivity for DA detection. The controlled deposition of the ErGO/MWCNTs/PPy nanocomposites can provide enhanced electrochemical detection of DA. The sensor demonstrates a short time response within 2 s and is a highly sensitive approach for DA detection with a dynamic linear range of 25–1000 nM (R2 = 0.999). The detection limit is estimated to be 2.3 nM, and the sensor sensitivity is calculated to be 8.96 μA μM−1 cm−2, with no distinct responses observed for other biological molecules. [ABSTRACT FROM AUTHOR]