Dec 22, 2016

Downregulation of Homer1b/c in SOD1 G93A Models of ALS: A Novel Mechanism of Neuroprotective Effect of Lithium and Valproic Acid

International Journal of Molecular Sciences
Hai-Zhi JiangHong-Lin Feng

Abstract

Mutations in the Cu/Zn superoxide dismutase (SOD1) gene have been linked to amyotrophic lateral sclerosis (ALS). However, the molecular mechanisms have not been elucidated yet. Homer family protein Homer1b/c is expressed widely in the central nervous system and plays important roles in neurological diseases. In this study, we explored whether Homer1b/c was involved in SOD1 mutation-linked ALS. In vitro studies showed that the SOD1 G93A mutation induced an increase of Homer1b/c expression at both the mRNA and protein levels in NSC34 cells. Knockdown of Homer1b/c expression using its short interfering RNA (siRNA) (si-Homer1) protected SOD1 G93A NSC34 cells from apoptosis. The expressions of Homer1b/c and apoptosis-related protein Bax were also suppressed, while Bcl-2 was increased by lithium and valproic acid (VPA) in SOD1 G93A NSC34 cells. In vivo, both the mRNA and protein levels of Homer1b/c were increased significantly in the lumbar spinal cord in SOD1 G93A transgenic mice compared with wild type (WT) mice. Moreover, lithium and VPA treatment suppressed the expression of Homer1b/c in SOD1 G93A mice. The suppression of SOD1 G93A mutation-induced Homer1b/c upregulation protected ALS against neuronal apoptosis, which is a novel ...Continue Reading

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Mentioned in this Paper

Study
In Vivo
Pathogenic Aspects
Pathogenesis
Apoptosis, Intrinsic Pathway
Gene Knockdown Techniques
HOMER1 protein, human
Genes
Entire Lumbar Spinal Cord
RNA, Small Interfering

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