Abnormal
            <scp>TDP</scp>
            ‐43 function impairs activity‐dependent
            <scp>BDNF</scp>
            secretion, synaptic plasticity, and cognitive behavior through altered Sortilin splicing

Tann, Jason Y.; Wong, Lik-Wei; Sajikumar, Sreedharan; Ibáñez, Carlos F.

doi:10.15252/embj.2018100989

Cited by 32 publications

(19 citation statements)

References 51 publications

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“…Loss of TDP-43 leads to the generation of isoform owing to additional exon 17b and soluble Sortilin protein. Therefore, a study by Tann et al hypothesized that TDP-43 dysfunction caused by mutations in TARDBP gene altered BDNF secretion and synaptic plasticity [77]. In a mouse model, the authors confirmed that hippocampal CA1-specific knockout of TDP-43 increased exon 17b mRNA of sort1 mRNA and reduced dendrite complexity and spine.…”

Section: Tar-binding Protein Gene (Tardbp)mentioning

confidence: 93%

CRISPR/Cas9-Mediated Gene Correction to Understand ALS

Yun

2020

IJMS

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by the death of motor neurons in the spinal cord and brainstem. ALS has a diverse genetic origin; at least 20 genes have been shown to be related to ALS. Most familial and sporadic cases of ALS are caused by variants of the SOD1, C9orf72, FUS, and TARDBP genes. Genome editing using clustered regularly interspaced short palindromic repeats/CRISPR-associated system 9 (CRISPR/Cas9) can provide insights into the underlying genetics and pathophysiology of ALS. By correcting common mutations associated with ALS in animal models and patient-derived induced pluripotent stem cells (iPSCs), CRISPR/Cas9 has been used to verify the effects of ALS-associated mutations and observe phenotype differences between patient-derived and gene-corrected iPSCs. This technology has also been used to create mutations to investigate the pathophysiology of ALS. Here, we review recent studies that have used CRISPR/Cas9 to understand the genetic underpinnings of ALS.

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Section: Tar-binding Protein Gene (Tardbp)mentioning

confidence: 93%

CRISPR/Cas9-Mediated Gene Correction to Understand ALS

Yun

2020

IJMS

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“…It has a known role in regulating brain-derived neurotrophic factor (BDNF), which is essential for synaptic plasticity, neuronal survival as well as differentiation [127]. Tann et al ( 2019) successfully corrected M337V mutation in TDP-43 M337V -iPSCs using CRISPR/Cas9 and proved that M337V mutation impairs BDNF secretion and synaptic plasticity through altering Sortilin splicing [128]. Gene editing using CRISPR/Cas9 has opened a new avenue of therapeutic approach for ALS.…”

Section: Targeting Tardbpmentioning

confidence: 99%

Gene Therapy in Amyotrophic Lateral Sclerosis

Fang

Pacut

et al. 2022

Cells

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Since the discovery of Cu/Zn superoxide dismutase (SOD1) gene mutation, in 1993, as the first genetic abnormality in amyotrophic lateral sclerosis (ALS), over 50 genes have been identified as either cause or modifier in ALS and ALS/frontotemporal dementia (FTD) spectrum disease. Mutations in C9orf72, SOD1, TAR DNA binding protein 43 (TARDBP), and fused in sarcoma (FUS) genes are the four most common ones. During the last three decades, tremendous effort has been made worldwide to reveal biological pathways underlying the pathogenesis of these gene mutations in ALS/FTD. Accordingly, targeting etiologic genes (i.e., gene therapies) to suppress their toxic effects have been investigated widely. It includes four major strategies: (i) removal or inhibition of abnormal transcribed RNA using microRNA or antisense oligonucleotides (ASOs), (ii) degradation of abnormal mRNA using RNA interference (RNAi), (iii) decrease or inhibition of mutant proteins (e.g., using antibodies against misfolded proteins), and (iv) DNA genome editing with methods such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas). The promising results of these studies have led to the application of some of these strategies into ALS clinical trials, especially for C9orf72 and SOD1. In this paper, we will overview advances in gene therapy in ALS/FTD, focusing on C9orf72, SOD1, TARDBP, and FUS genes.

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“…Previous studies showed that these four genes [MADD (38), STAG2 (39), FNIP1 (40), and BRD8 (41)] were potentially important for tumors. In mice models, abnormal TDP-43 function, owing to aggregation or diseaseassociated mutation, induced the wrong splicing of trafficking receptor sortilin (42), the loss of which promoted cell proliferation of lung cancer cells (43). Similarly, TDP-43 also regulated lncRNA expression.…”

Section: Tdp-43-mediated Mrna Splicingmentioning

confidence: 99%

The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer

Ying

Xie

et al. 2021

Front. Oncol.

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TAR-DNA-binding protein-43 (TDP-43) is a member of hnRNP family and acts as both RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation in various diseases. Currently, emerging evidence gradually elucidates the crucial role of TDP-43 in human cancers like it is previously widely researched in neurodegeneration diseases. A series of RNA metabolism events, including mRNA alternative splicing, transport, stability, miRNA processing, and ncRNA regulation, are all confirmed to be closely involved in various carcinogenesis and tumor progressions, which are all partially regulated and interacted by TDP-43. Herein we conducted the first overall review about TDP-43 and cancers to systematically summarize the function and precise mechanism of TDP-43 in different human cancers. We hope it would provide basic knowledge and concepts for tumor target therapy and biomarker diagnosis in the future.

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Abnormal TDP ‐43 function impairs activity‐dependent BDNF secretion, synaptic plasticity, and cognitive behavior through altered Sortilin splicing

Cited by 32 publications

References 51 publications

CRISPR/Cas9-Mediated Gene Correction to Understand ALS

CRISPR/Cas9-Mediated Gene Correction to Understand ALS

Gene Therapy in Amyotrophic Lateral Sclerosis

The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer

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