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A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stress

Hanan, Mor, Simchovitz, Alon, Yayon, Nadav, Vaknine, Shani, Cohen‐Fultheim, Roni, Karmon, Miriam, Madrer, Nimrod, Rohrlich, Talia Miriam, Maman, Moria, Bennett, Estelle R, Greenberg, David S, Meshorer, Eran, Levanon, Erez Y, Soreq, Hermona, Kadener, Sebastian·2020·EMBO Molecular Medicine
DOI 10.15252/emmm.201911942PMC PMC7507321
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Abstract

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.

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Metadata

Authors
Hanan, M., Simchovitz, A., Yayon, N., Vaknine, S., Cohen‐Fultheim, R., Karmon, M., Madrer, N., Rohrlich, T. M., Maman, M., Bennett, E. R., Greenberg, D. S., Meshorer, E., Levanon, E. Y., Soreq, H., & Kadener, S.
ORCID
Venue
EMBO Molecular Medicine
Publisher
Springer Science and Business Media LLC
Published
2020-07-26
Volume
12
Issue
9
ISSN
  • 1757-4676
  • 1757-4684
DOI
10.15252/emmm.201911942
PMC
PMC7507321
Cited by
130
References
17
Language
en
Update notices
Licence
Funders
  • Michael J. Fox Foundation for Parkinson's Research (MJFF11183)
  • The Netherlands Brain Bank
  • Israeli Ministry of Science, Technology and Space (53140)
  • Edmond and Lily Safra Center of Brain Sciences
  • National Institutes of Health (R01AG057700)

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