Overexpression of the X-Linked Inhibitor of Apoptosis Protein (XIAP) in Neurons Improves Cell Survival and the Functional Outcome After Traumatic Spinal Cord Injury

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2023 Feb 11

PMID 36769152

Authors

David Reigada

Rodrigo M Maza

Teresa Munoz-Galdeano

Maria Asuncion Barreda-Manso

Altea Soto

Dan Lindholm

Rosa Navarro-Ruiz

Manuel Nieto-Diaz

Affiliations

Soon will be listed here.

Abstract

Mechanical trauma to the spinal cord causes extensive neuronal death, contributing to the loss of sensory-motor and autonomic functions below the injury location. Apoptosis affects neurons after spinal cord injury (SCI) and is associated with increased caspase activity. Cleavage of X-linked inhibitor of apoptosis protein (XIAP) after SCI may contribute to this rise in caspase activity. Accordingly, we have shown that the elevation of XIAP resulted in increased neuronal survival after SCI and improved functional recovery. Therefore, we hypothesise that neuronal overexpression of XIAP can be neuroprotective after SCI with improved functional recovery. In line with this, studies of a transgenic mice with overexpression of XIAP in neurons revealed that higher levels of XIAP after spinal cord trauma favours neuronal survival, tissue preservation, and motor recovery after the spinal cord trauma. Using human SH-SY5Y cells overexpressing XIAP, we further showed that XIAP reduced caspase activity and apoptotic cell death after pro-apoptotic stimuli. In conclusion, this study shows that the levels of XIAP expression are an important factor for the outcome of spinal cord trauma and identifies XIAP as an important therapeutic target for alleviating the deleterious effects of SCI.

Citing Articles

E3 ubiquitination ligase XIAP lightens diabetes-induced cognitive impairment by inactivating TXNIP-ERS-mediated neuronal injury.

Zhang Q, Huang H, Zhang J, Tian Y, Hu Y Kaohsiung J Med Sci. 2024; 41(1):e12913.

PMID: 39629879 PMC: 11724162. DOI: 10.1002/kjm2.12913.

Identification of a New Role of miR-199a-5p as Factor Implied in Neuronal Damage: Decreasing the Expression of Its Target X-Linked Anti-Apoptotic Protein (XIAP) After SCI.

Munoz-Galdeano T, Reigada D, Soto A, Barreda-Manso M, Ruiz-Amezcua P, Nieto-Diaz M Int J Mol Sci. 2024; 25(22).

PMID: 39596440 PMC: 11594351. DOI: 10.3390/ijms252212374.

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