GSE211934
Pathological effects of SARS-CoV-2 and a-synuclein preformed fibril in hESC-derived dopaminergic neurons
Progression Parkinson's disease (PD) has been strongly correlated to concurrent virus infection such as herpes virus, Helicobacter pylori, hepatitis C, and pneumococcus and the concurrent immune response in the brain. However, the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the onset and progression of PD is yet to be investigated. As the pandemic is getting closer to being under control and majority of the population in the world will have been infected with SARS-CoV-2, there will be a huge need for uncovering the unknown, possible neurological sequelae of SARS-CoV-2 infection. Here we report that SARS-CoV-2 infection increased the susceptibility of DA neurons to PFF-induced cell death while PFF or SARS-CoV-2 alone did not exert a cytotoxic effect on dopaminergic (DA) neurons. RNA sequencing data revealed mechanistic investigations that SARS-CoV-2, in vitro, increased susceptibility to PFF-induced PD-like pathology including changes in expression of signaling molecules in apoptosis, autophagy, oxidative stress, and mitochondrial function. Thus, our study provides a previously unappreciated paradigm that SARS-CoV-2 infection persists in the brain and increases susceptibility to neurodegenerative diseases such as PD via continuous inflammatory response as a long-term sequela. Overall design: Biological replicates of hESC-derived dopaminergic neurons prepared under thoroughly isolated conditions were infected with SARS-CoV-2 along with treatment of a-synuclein preformed fibril, and each subset was analyzed.