MiR-33a is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons

Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here we show that SPAST , which encodes a microtubule-severing protein called spastin, was a novel target gene of miR-33 in human. Actually, the miR-33 binding site in the SPAST 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of miR-33 on SPAST in mice. We demonstrated that inhibition of miR-33a, a major form of miR-33 in human neurons, via locked nucleic acid-anti-miR (LNA) ameliorated the pathological phenotype in HSP-SPG4 patient iPSC-derived cortical neurons. Thus, miR-33a can be a potential therapeutic target for the treatment of HSP-SPG4.

Source: Clinical Science - February 18, 2019 Category: Biomedical Science Authors: Nakazeki, F., Tsuge, I., Horie, T., Imamura, K., Tsukita, K., Hotta, A., Baba, O., Kuwabara, Y., Nishino, T., Nakao, T., Nishiga, M., Nishi, H., Nakashima, Y., Ide, Y., Koyama, S., Kimura, M., Tsuji, S., Naitoh, M., Suzuki, S., Izumi, Y., Kawarai, T., Kaj Tags: PublishAheadOfPrint Source Type: research