ArticleThe Journal of clinical investigation2023
Reduction of nemo-like kinase increases lysosome biogenesis and ameliorates TDP-43-related neurodegeneration.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Advances and Challenges in Gene Therapy for Neurodegenerative Diseases: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Stress granules as a central hub linking organelle stress, aging, and neurodegeneration.BMB reports · 2026Review
- Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS.The Journal of clinical investigation · 2025Article
- MAPK Signaling in the Interplay Between Oxidative Stress and Autophagy.Antioxidants (Basel, Switzerland) · 2025Review
- Targeting chaperone-mediated autophagy in neurodegenerative diseases: mechanisms and therapeutic potential.Acta pharmacologica Sinica · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).Autophagy reports · 2025Review
- Progranulin deficiency does not exacerbate TDP-43 pathology in TDP-43 transgenic mouse models.NPJ dementia · 2025Article
- Two-sample Mendelian randomization analysis of 91 circulating inflammatory protein levels and amyotrophic lateral sclerosis.Frontiers in aging neuroscience · 2024Article
- Localized T3 production modifies the transcriptome and promotes the hepatocyte-like lineage in iPSC-derived hepatic organoids.JCI insight · 2023Article
- Microglia regulate brain progranulin levels through the endocytosis/lysosomal pathway.JCI insight · 2021Article
Corrections and comments
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Authors and funding
20 authors at 3 institutions in 1 country.
Funding
Abstract
Protein aggregation is a hallmark of many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Although mutations in TARDBP, encoding transactive response DNA-binding protein 43 kDa (TDP-43), account for less than 1% of all ALS cases, TDP-43-positive aggregates are present in nearly all ALS patients, including patients with sporadic ALS (sALS) or carrying other familial ALS-causing (fALS-causing) mutations. Interestingly, TDP-43 inclusions are also present in subsets of patients with frontotemporal dementia, Alzheimer's disease, and Parkinson's disease; therefore, methods of activating intracellular protein quality control machinery capable of clearing toxic cytoplasmic TDP-43 species may alleviate disease-related phenotypes. Here, we identify a function of nemo-like kinase (Nlk) as a negative regulator of lysosome biogenesis. Genetic or pharmacological reduction of Nlk increased lysosome formation and improved clearance of aggregated TDP-43. Furthermore, Nlk reduction ameliorated pathological, behavioral, and life span deficits in 2 distinct mouse models of TDP-43 proteinopathy. Because many toxic proteins can be cleared through the autophagy/lysosome pathway, targeted reduction of Nlk represents a potential approach to therapy development for multiple neurodegenerative disorders.
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Registered trials
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