2 research outputs found
A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress
Abstract Circular RNAs (circRNAs) are brainâabundant RNAs of mostly unknown functions. To seek their roles in Parkinson's disease (PD), we generated an RNA sequencing resource of several brain region tissues from dozens of PD and control donors. In the healthy substantia nigra (SN), circRNAs accumulate in an ageâdependent manner, but in the PD SN this correlation is lost and the total number of circRNAs reduced. In contrast, the levels of circRNAs are increased in the other studied brain regions of PD patients. We also found circSLC8A1 to increase in the SN of PD individuals. CircSLC8A1 carries 7 binding sites for miRâ128 and is strongly bound to the microRNA effector protein Ago2. Indeed, RNA targets of miRâ128 are also increased in PD individuals, suggesting that circSLC8A1 regulates miRâ128 function and/or activity. CircSLC8A1 levels also increased in cultured cells exposed to the oxidative stressâinducing agent paraquat but were decreased in cells treated with the neuroprotective antioxidant regulator drug Simvastatin. Together, our work links circSLC8A1 to oxidative stressârelated Parkinsonism and suggests further exploration of its molecular function in PD
A Parkinsonâs disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress
Abstract Circular RNAs (circRNAs) are brainâabundant RNAs of mostly unknown functions. To seek their roles in Parkinson's disease (PD), we generated an RNA sequencing resource of several brain region tissues from dozens of PD and control donors. In the healthy substantia nigra (SN), circRNAs accumulate in an ageâdependent manner, but in the PD SN this correlation is lost and the total number of circRNAs reduced. In contrast, the levels of circRNAs are increased in the other studied brain regions of PD patients. We also found circSLC8A1 to increase in the SN of PD individuals. CircSLC8A1 carries 7 binding sites for miRâ128 and is strongly bound to the microRNA effector protein Ago2. Indeed, RNA targets of miRâ128 are also increased in PD individuals, suggesting that circSLC8A1 regulates miRâ128 function and/or activity. CircSLC8A1 levels also increased in cultured cells exposed to the oxidative stressâinducing agent paraquat but were decreased in cells treated with the neuroprotective antioxidant regulator drug Simvastatin. Together, our work links circSLC8A1 to oxidative stressârelated Parkinsonism and suggests further exploration of its molecular function in PD