ArticleNature communications2024
TDP-43 proteinopathy in ALS is triggered by loss of ASRGL1 and associated with HML-2 expression.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Downregulation of miRNAs Accompanies Increased HERV-K (HML-2) Expression in Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2026Article
- Fructose-2,6-bisphosphate restores TDP-43 pathology-driven genome repair deficiency in motor neuron diseases.Communications biology · 2026Article
- NeuroViOme: a viral orfeome collection for studies of neurodegenerative disease.Journal of neurovirology · 2026Review
- High-throughput multi-organ proteomics workflow for drug efficacy and toxicity analysis.Nature communications · 2026Article
- Asparaginase-like protein 1 and human endogenous retroviruses link immune and gene dysregulation in dementia.Frontiers in cellular and infection microbiology · 2026Article
- Single-Cell-Derived Malignant Epithelial Programs Define Prognostic Risk and Therapeutic Vulnerability in Ovarian Cancer.Journal of Cancer · 2026Article
- Antibody screening identifies HERV-K-related immune responses as candidate biomarkers in Parkinson's disease.Frontiers in cellular and infection microbiology · 2026Article
- Microbiota-host crosstalk: the role of short-term dietary restriction in neurological and metabolic dysregulation.NPJ biofilms and microbiomes · 2025Article
- Inhibition of Casein Kinase 1International journal of molecular sciences · 2025Article
- Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease.Nature reviews. Molecular cell biology · 2025Review
- Human Endogenous Retroviruses as Novel Therapeutic Targets in Neurodegenerative Disorders.Vaccines · 2025Review
- A Characterization of the Humoral Immune Response to Human Endogenous Retroviruses andPathogens (Basel, Switzerland) · 2025Article
- Neurotropic Viruses as Acute and Insidious Drivers of Aging.Biomolecules · 2025Review
- Retrotransposon: an insight into neurological disorders from perspectives of neurodevelopment and aging.Translational neurodegeneration · 2025Review
- An integrated approach for the accurate detection of HERV-K HML-2 transcription and protein synthesis.Nucleic acids research · 2025Article
- Upregulation of microRNAs correlates with downregulation of HERV-K expression in Parkinson's disease.Journal of neurovirology · 2024Article
- Review
- The Humoral Immune Response against Human Endogenous Retroviruses in Celiac Disease: A Case-Control Study.Biomedicines · 2024Article
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Authors and funding
27 authors.
Funding
Abstract
TAR DNA-binding protein 43 (TDP-43) proteinopathy in brain cells is the hallmark of amyotrophic lateral sclerosis (ALS) but its cause remains elusive. Asparaginase-like-1 protein (ASRGL1) cleaves isoaspartates, which alter protein folding and susceptibility to proteolysis. ASRGL1 gene harbors a copy of the human endogenous retrovirus HML-2, whose overexpression contributes to ALS pathogenesis. Here we show that ASRGL1 expression was diminished in ALS brain samples by RNA sequencing, immunohistochemistry, and western blotting. TDP-43 and ASRGL1 colocalized in neurons but, in the absence of ASRGL1, TDP-43 aggregated in the cytoplasm. TDP-43 was found to be prone to isoaspartate formation and a substrate for ASRGL1. ASRGL1 silencing triggered accumulation of misfolded, fragmented, phosphorylated and mislocalized TDP-43 in cultured neurons and motor cortex of female mice. Overexpression of ASRGL1 restored neuronal viability. Overexpression of HML-2 led to ASRGL1 silencing. Loss of ASRGL1 leading to TDP-43 aggregation may be a critical mechanism in ALS pathophysiology.
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