Caffeic acid reduces A53T α-synuclein by activating JNK/Bcl-2-mediated autophagy in vitro and improves behaviour and protects dopaminergic neurons in a mouse model of Parkinson’s disease

Publication date: Available online 9 November 2019Source: Pharmacological ResearchAuthor(s): Yu Zhang, Qimei Wu, Lei Zhang, Qing Wang, Zexian Yang, Jia Liu, Linyin FengAbstractThe human A53 T mutant of α-synuclein tends to aggregate and leads to neurotoxicity in familial Parkinson's disease (PD). The aggregation of α-synuclein is also found in sporadic PD. Thus, targeting α-synuclein clearance could be used as a drug-discovery strategy for PD treatment. Caffeic acid (CA) has shown neuroprotection in Alzheimer's disease or cerebral ischaemia; however, it is unclear whether CA confers neuroprotection in α-synuclein-induced PD models. Here we focus on whether and how A53 T α-synuclein is affected by ca. We assessed the effect of CA on cell viability in SH-SY5Y cells overexpressing A53 T α-synuclein. Pathway-related inhibitors were used to identify the autophagy mechanisms. Seven-month-old A53 T α-synuclein transgenic mice (A53 T Tg mice) received CA daily for eight consecutive weeks. Behaviour tests including the buried food pellet test, the pole test, the Rotarod test, open field analysis, and gait analysis were used to evaluate the neuroprotective effect of ca. Tyrosine hydroxylase and α-synuclein were assessed by immunohistochemistry or western blot in the substantia nigra (SN). We found that CA alleviated the cell damage induced by overexpressing A53 T α-synuclein and that CA reduced A53 T α-synuclein by activating the JNK/Bcl-2-mediated autophagy pat...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research