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Kaya et al. Neuroimmunol Neuroinflammation 2019;6:5 Neuroimmunology and
DOI: 10.20517/2347-8659.2018.70 Neuroinflammation

Review Open Access

Speedy/RINGO: a molecular savior in spinal cord
injury-based neurodegeneration?

Yesim Kaya, Aysegul Yildiz

Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman University, Kotekli, Mentese, Mugla 48000,
Turkey.

Correspondence to: Dr. Aysegul Yildiz, Department of Molecular Biology and Genetics, Faculty of Science, Mugla Sitki Kocman
University, Kotekli, Mentese, Mugla 48000, Turkey. E-mail: aysegulunal@mu.edu.tr
How to cite this article: Kaya Y, Yildiz A. Speedy/RINGO: a molecular savior in spinal cord injury-based neurodegeneration?
Neuroimmunol Neuroinflammation 2019;6:5. http://dx.doi.org/10.20517/2347-8659.2018.70
Received: 20 Dec 2018 First Decision: 19 Feb 2019 Revised: 28 Feb 2019 Accepted: 9 Mar 2019 Published: 28 Mar 2019

Science Editor: Swapan K. Ray Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Endogenous or exogenous insults can cause spinal cord injury (SCI), often resulting in the loss of motor, autonomic,
sensory and reflex functions. The pathogenesis of SCI comprises two stages. The primary injury stage occurs at the
moment of trauma and is characterized by hemorrhage and rapid cell death. The secondary injury stage occurs due to
progression of primary damage and is characterized by tissue loss and functional disorder. One of the most important
cellular mechanisms underlying secondary injury is glutamate excitotoxicity, which overactivates the calpain protease
2+
2+
via excessive Ca influx and induces neuronal apoptosis via p53 induction. Furthermore, Ca influx elicits apoptosis
by inducing p53, thus negatively affecting two pathways: the mitogenic extracellular signal-regulated kinase/mitogen-
activated protein kinase (ERK/MAPK) pathway and the survival phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)
pathway. Speedy/rapid inducer of G2/M progression in oocytes (Speedy/RINGO) is a cell cycle regulatory protein that
increases survival of p53-positive mitotic cells by inhibiting the apoptotic machinery. Moreover, this protein elicits p53-
dependent anti-apoptotic effects on calpain-induced degeneration of primary hippocampal neurons, amyotrophic lateral
sclerosis motor neurons, and astrocytes and microglia in spinal cord lesions. The pathophysiology of SCI has not been
fully elucidated and this hinders the development of powerful therapeutic strategies. This review focuses on the cellular
mechanisms underlying the anti-apoptotic effects of Speedy/RINGO and discusses how this protective function can
possibly be exploited to facilitate recovery from SCI. Particular attention is paid to reversal of the negative effects on the
ERK/MAPK and PI3K/AKT pathways via induction of p53.

Keywords: Speedy/RINGO, calpain, p53, extracellular signal-regulated kinase/mitogen-activated protein kinase,
phosphoinositide 3-kinase/protein kinase B, spinal cord injury, glutamate excitotoxicity, calcium influx

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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