ArticleClinical and translational medicine2022
Cracking the cryptic code in amyotrophic lateral sclerosis and frontotemporal dementia: Towards therapeutic targets and biomarkers.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 27 citations in OpenAlex.
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Molecular signatures and biomarker development for limbic-predominant age-related TDP-43 encephalopathy (LATE).Acta neuropathologica · 2026Review
- Article
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.Nature neuroscience · 2025Article
- Pathogenic UNC13A variants cause a neurodevelopmental syndrome by impairing synaptic function.Nature genetics · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Article
- Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.Muscle & nerve · 2025Review
- Emerging biomarkers in amyotrophic lateral sclerosis: from pathogenesis to clinical applications.Frontiers in molecular biosciences · 2025Review
- Abnormal Splicing Events due to Loss of Nuclear Function of TDP-43: Pathophysiology and Perspectives.JMA journal · 2024Review
- The new missense G376V-TDP-43 variant induces late-onset distal myopathy but not amyotrophic lateral sclerosis.Brain : a journal of neurology · 2024Article
- RNA aptamer reveals nuclear TDP-43 pathology is an early aggregation event that coincides with STMN-2 cryptic splicing and precedes clinical manifestation in ALS.Acta neuropathologica · 2024Article
- TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes.bioRxiv : the preprint server for biology · 2024Article
- Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2024Article
- Biomarkers in amyotrophic lateral sclerosis: current status and future prospects.Nature reviews. Neurology · 2023Review
- Cryptic exon detection and transcriptomic changes revealed in single-nuclei RNA sequencing of C9ORF72 patients spanning the ALS-FTD spectrum.Acta neuropathologica · 2023Article
- Granulin loss of function in human mature brain organoids implicates astrocytes in TDP-43 pathology.Stem cell reports · 2023Article
- Six genetically linked mutations in the CD36 gene significantly delay the onset of Alzheimer's disease.Scientific reports · 2022Article
- Cracking the cryptic code in amyotrophic lateral sclerosis and frontotemporal dementia: Towards therapeutic targets and biomarkers.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two devastating human neurodegenerative diseases. A hallmark pathological feature of both diseases is the depletion of the RNA-binding protein TDP-43 from the nucleus in the brain and spinal cord of patients. A major function of TDP-43 is to repress the inclusion of cryptic exons during RNA splicing. When it becomes depleted from the nucleus in disease, this function is lost, and recently, several key cryptic splicing targets of TDP-43 have emerged, including STMN2, UNC13A, and others. UNC13A is a major ALS/FTD risk gene, and the genetic variations that increase the risk for disease seem to do so by making the gene more susceptible to cryptic exon inclusion when TDP-43 function is impaired. Here, we discuss the prospects and challenges of harnessing these cryptic splicing events as novel therapeutic targets and biomarkers. Deciphering this new cryptic code may be a touchstone for ALS and FTD diagnosis and treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.