Pathomechanism characterization and potential therapeutics identification for SCA3 targeting neuroinflammation
Ya‐Jen Chiu, Shu-An Lin, Wan-Ling Chen, Te‐Hsien Lin, Chih‐Hsin Lin, Ching‐Fa Yao, Wenwei Lin, Yih‐Ru Wu, Kuo‐Hsuan Chang, Guey‐Jen Lee‐Chen, Chiung‐Mei Chen
Abstract
-GFP SH-SY5Y cells inflamed with IFN-γ-primed HMC3 conditioned medium, treatment with the tested compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced polyQ aggregation and ROS and/or promoted neurite outgrowth. Examination of IL-1β- and TNF-α-mediated signaling pathways revealed that the tested compounds decreased IκBα/P65, JNK/JUN and/or P38/STAT1 signaling. The study results suggest the potential of NC009-1, AM404, VB-037 and LM-031 in treating SCA3 and probable other polyQ diseases.
Topics & Concepts
NeuroinflammationIdentification (biology)Computational biologyChemistryNeuroscienceBiologyImmunologyInflammationEcologyGenetic Neurodegenerative DiseasesUbiquitin and proteasome pathwaysHereditary Neurological Disorders