Soreq's Lab: Paper of the Month, October 2020

1st Paper

Alon Simchovitz-Gesher, Hermona Soreq
Pharmaceutical Implications of Sex-Related RNA Divergence in Psychiatric Disorders, Trends in Pharmacological Sciences, Volume 41, Issue 11, 2020, Pages 840-850, ISSN 0165-6147


Lay summary:
Psychiatric disorders have long been known to differ between men and women. The age when the symptoms emerge, the type of symptoms, and their severity. Even the incidence show differences such that men, much more than women, with schizophrenia tend to get addicted to nicotine, and women respond poorly to the commonly prescribed Alzheimer’s disease drugs. However, the origin and scope of those differences remained incompletely understood. In this review, we cover the impact of sex-related hormones and the sex-specific chromosomes on the differences in response to therapeutics between men and women with mental diseases and highlight the importance of studying the origins of these differences and the potential ways to address them for improving human health and wellbeing. Specifically, we describe the pharmacokinetics differences, the distinct side effects and the sex-specific drug efficacy, and cover the reasons for the emergence of those distinctions in the course of sex-biased pre-clinical research and clinical trials.




2nd Paper

Mor Hanan, Alon Simchovitz, Nadav Yayon, Shani Vaknine, Roni Cohen‐Fultheim, Miriam Karmon, Nimrod Madrer, Talia Miriam Rohrlich, Moria Maman, Estelle R Bennett, David S Greenberg, Eran Meshorer, Erez Y Levanon, Hermona Soreq, Sebastian Kadener
A Parkinson's disease CircRNAs Resource reveals a link between circSLC8A1 and oxidative stressEMBO Mol Med (2020) 12: e11942


Lay summary:
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 from dozens of PD patients 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 brain regions of PD patients. The paper describes additional findings about other circRNAs like circSLC8A1. We suggest that circSLC8A1 regulates the function of miR-128. Further, circSLC8A1 levels increased in cultured cells exposed to the oxidative stress-inducing agent and were sensitive to specific drugs. Together, our work links circSLC8A1 to oxidative stress-related Parkinsonism and suggests further exploration of its molecular function in PD.