Targeting the RNA-Binding Protein HuR as Potential Thera-Peutic Approach for Neurological Disorders: Focus on Amyo-Trophic Lateral Sclerosis (ALS), Spinal Muscle Atrophy (SMA) and Multiple Sclerosis

Abstract

The importance of precise co- and post-transcriptional processing of RNA in the regulation of gene expression has become increasingly clear. RNA-binding proteins (RBPs) are a class of proteins that bind single- or double-chain RNA, with different affinities and selectivity, thus regulating the various functions of RNA and the fate of the cells themselves. ELAV (embryonic lethal/abnormal visual system)/Hu proteins represent an important family of RBPs and play a key role in the fate of newly transcribed mRNA. ELAV proteins bind AU-rich element (ARE)-containing transcripts, which are usually present on the mRNA of proteins such as cytokines, growth factors, and other proteins involved in neuronal differentiation and maintenance. In this review, we focused on a member of ELAV/Hu proteins, HuR, and its role in the development of neurodegenerative disorders, with a particular focus on demyelinating diseases.

Posttranscriptional Regulation of Gene Expression Participates in the Myelin Restoration in Mouse Models of Multiple Sclerosis: Antisense Modulation of HuR and HuD ELAV RNA Binding Protein

“…HuR is an ubiquitous protein that, besides neurons, is expressed in activated microglia [19,20], and it is involved in cytoplasmic stabilization and/or enhancement of translation of mRNA of pro-inflammatory mediators, representing an important regulator of inflammatory and immune processes [21]. A pathological role for HuR in neuroinflammatory disorders has emerged, and its involvement in the pathogenesis of neurodegenerative and demyelinating disease has been postulated [22]. HuB, HuC, and HuD are neuron-specific proteins involved in neuronal differentiation, axonal outgrowth, and neuronal integrity [23].…”

Alterations of RNA-binding protein found in neurons in Drosophila neurons and glia influence synaptic transmission and lifespan

“…Defects in ELAVL2/HuB, ELAVL4/HuD, and their target transcripts can lead to abnormal neuronal proliferation and development and result in the pathogenesis of numerous CNS disorders, including seizures, autism, and schizophrenia (Yamada et al, 2011;Bronicki and Jasmin, 2013;Berto et al, 2016;Zybura-Broda et al, 2018). Silencing ELAVL1/HuR, which also shares high amino acid identity with FNE (Samson and Chalvet, 2003) in the activated microglia and astrocytes attenuate neuroinflammation and the occurrence of amyotrophic lateral sclerosis (Borgonetti et al, 2021). Thus, we conducted a bioinformatic analysis of ELAVL2/HuB and ELAVL4/HuD in neurons and glia from published gene expression datasets of human, mice, and rat samples.…”

MCD Diet Modulates HuR and Oxidative Stress-Related HuR Targets in Rats

“…The human antigen R (HuR; a.k.a. ELAVL-1/ELAV), is an ubiquitously expressed RBP that has been implicated in a plethora of conditions, including cancer [ 23 ], atherosclerosis [ 24 ], pulmonary fibrosis [ 25 ], and neurological disorders [ 26 , 27 ]. Recently, several studies have also considered its role in NAFLD, discovering that HuR exerts a protective role by targeting glucose and lipid metabolism [ 28 , 29 ].…”