ArticleStem cell reports2022
Loss of endosomal exchanger NHE6 leads to pathological changes in tau in human neurons.
Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- Cellular Models of Aging and Senescence.Cells · 2025Review
- A Cautionary Note on the Indication for Deep Brain Stimulation in Parkinsonism Patients With SLC9A6 Gene Mutations.Journal of movement disorders · 2025Article
- Article
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Christianson syndrome across the lifespan: genetic mutations and longitudinal study in children, adolescents, and adults.Journal of medical genetics · 2024Article
- Metformin Lysosomal Targeting: A Novel Aspect to Be Investigated for Metformin Repurposing in Neurodegenerative Diseases?International journal of molecular sciences · 2024Review
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Genetic forms of tauopathies: inherited causes and implications of Alzheimer's disease-like TAU pathology in primary and secondary tauopathies.Journal of neurology · 2024Review
- Targeting NHE6 gene expression identifies lysosome and neurodevelopmental mechanisms in a haploid in vitro cell model.Biology open · 2023Article
- Tau accumulation in degradative organelles is associated to lysosomal stress.Scientific reports · 2023Article
- Editorial:Pathology oncology research : POR · 2023Article
- Clinical and genetic analysis of Christianson syndrome caused by variant ofFrontiers in neurology · 2023Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Disruption of endolysosomal and autophagy-lysosomal systems is increasingly implicated in neurodegeneration. Sodium-proton exchanger 6 (NHE6) contributes to the maintenance of proper endosomal pH, and loss-of function mutations in the X-linked NHE6 lead to Christianson syndrome (CS) in males. Neurodegenerative features of CS are increasingly recognized, with postmortem and clinical data implicating a role for tau. We generated cortical neurons from NHE6 knockout (KO) and isogenic wild-type control human induced pluripotent stem cells. We report elevated phosphorylated and sarkosyl-insoluble tau in NHE6 KO neurons. We demonstrate that NHE6 KO leads to lysosomal and autophagy dysfunction involving reduced lysosomal number and protease activity, diminished autophagic flux, and p62 accumulation. Finally, we show that treatment with trehalose or rapamycin, two enhancers of autophagy-lysosomal function, each partially rescue this tau phenotype. We provide insight into the neurodegenerative processes underlying NHE6 loss of function and into the broader role of the endosome-lysosome-autophagy network in neurodegeneration.
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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.