A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress.
A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress.
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DOI：
10.15252/emmm.201911942
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发表时间：
2020-09-07
影响因子：
11.1
通讯作者：
Kadener S
中科院分区：
文献类型：
--
作者：
Hanan M;Simchovitz A;Yayon N;Vaknine S;Cohen-Fultheim R;Karmon M;Madrer N;Rohrlich TM;Maman M;Bennett ER;Greenberg DS;Meshorer E;Levanon EY;Soreq H;Kadener S
Circular RNAs (circRNAs) are brain‐abundant 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 age‐dependent 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 miR‐128 and is strongly bound to the microRNA effector protein Ago2. Indeed, RNA targets of miR‐128 are also increased in PD individuals, suggesting that circSLC8A1 regulates miR‐128 function and/or activity. CircSLC8A1 levels also increased in cultured cells exposed to the oxidative stress‐inducing agent paraquat but were decreased in cells treated with the neuroprotective antioxidant regulator drug Simvastatin. Together, our work links circSLC8A1 to oxidative stress‐related Parkinsonism and suggests further exploration of its molecular function in PD. In human brains, circRNA levels are region specific and inversely correlate to editing. In PD circRNAs are reduced in SN and accumulation correlation with age is lost. CircSLC8A1 increases in PD and oxidation, is bound to Ago2 and sponges miR128 targets, modulating neuronal survival and aging.
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影响因子：
16.2
作者：
Edbauer, Dieter;Neilson, Joel R.;Foster, Kelly A.;Wang, Chi-Fong;Seeburg, Daniel P.;Batterton, Matthew N.;Tada, Tomoko;Dolan, Bridget M.;Sharp, Phillip A.;Sheng, Morgan
通讯作者：
Sheng, Morgan
影响因子：
64.8
作者：
Aktas, Tugce;Ilik, Ibrahim Avsar;Akhtar, Asifa
通讯作者：
Akhtar, Asifa
DOI：
10.1126/science.aam9080
发表时间：
2017-09-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Burbulla LF;Song P;Mazzulli JR;Zampese E;Wong YC;Jeon S;Santos DP;Blanz J;Obermaier CD;Strojny C;Savas JN;Kiskinis E;Zhuang X;Krüger R;Surmeier DJ;Krainc D
通讯作者：
Krainc D
影响因子：
2.9
作者：
Briggs CE;Wang Y;Kong B;Woo TU;Iyer LK;Sonntag KC
通讯作者：
Sonntag KC
影响因子：
4.6
作者：
Gruner H;Cortés-López M;Cooper DA;Bauer M;Miura P
通讯作者：
Miura P