Abstract
Current treatments for neurodegenerative diseases (ND) are symptomatic and do not affect disease progression. Slowing this progression remains a crucial unmet need for patients and their families. c-Jun N-terminal kinase 3 (JNK3) are related to several ND hallmarks including apoptosis, oxidative stress, excitotoxicity, mitochondrial dysfunction, and neuroinflammation. JNK inhibitors can play an important role in addressing neuroprotection. This research aims to evaluate the neuroprotective, anti-inflammatory, and antioxidant effects of a synthetic compound (FMU200) with known JNK3 inhibitory activity in SH-SY5Y and RAW264.7 cell lines. SH-SY5Y cells were pretreated with FMU200 and cell damage was induced by 6-hydroxydopamine (6-OHDA) or hydrogen peroxide (H2O2). Cell viability and neuroprotective effect were assessed with an MTT assay. Flow cytometric analysis was performed to evaluate cell apoptosis. The H2O2-induced reactive oxygen species (ROS) generation and mitochondrial membrane potential (ΔΨm) were evaluated by DCFDA and JC-1 assays, respectively. The anti-inflammatory effect was determined in LPS-induced RAW264.7 cells by ELISA assay. In undifferentiated SH-SY5Y cells, FMU200 decreased neurotoxicity induced by 6-OHDA in approximately 20%. In RA-differentiated cells, FMU200 diminished cell death in approximately 40% and 90% after 24 and 48 h treatment, respectively. FMU200 reduced both early and late apoptotic cells, decreased ROS levels, restored mitochondrial membrane potential, and downregulated JNK phosphorylation after H2O2 exposure. In LPS-stimulated RAW264.7 cells, FMU200 reduced TNF-α levels after a 3 h treatment. FMU200 protects neuroblastoma SH-SY5Y cells against 6-OHDA- and H2O2-induced apoptosis, which may result from suppressing the JNK pathways. Our findings show that FMU200 can be a useful candidate for the treatment of neurodegenerative disorders.
Highlights
In neurodegenerative disorders (ND), such as Alzheimer’s disease (AD), it is common that neurons start degenerating during a prolonged preclinical period, where individuals are by definition asymptomatic and cognitively normal [1]
SH-SY5Y cells were more sensitive to compound-induced toxicity than SK-N-SH cells, the parental cell line of the SH-SY5Y cells [33]
An inflammatory model was successfully established using LPSstimulated RAW264.7 cells, and we investigated the effect of FMU200 on the levels of IL-10, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells
Summary
In neurodegenerative disorders (ND), such as Alzheimer’s disease (AD), it is common that neurons start degenerating during a prolonged preclinical period, where individuals are by definition asymptomatic and cognitively normal [1]. Researchers have put more effort into understanding neurodegenerative diseases and investing in patient management based on molecular approaches with potential disease-specific and/or disease-modifying treatments targeting neuroprotection. Neuroprotection can be characterized as a substantial and lasting slowdown in the disease’s progression associated with a delay in neuronal degeneration [2]. While a few drugs can improve the patient’s quality of life, there is neither a cure nor a disease-modifying drug for treating
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
