ReviewFrontiers in cellular neuroscience2014
An inside job: how endosomal Na(+)/H(+) exchangers link to autism and neurological disease.
Review in Frontiers in cellular neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- Histone deacetylase-mediated regulation of endolysosomal pH.The Journal of biological chemistry · 2018Pooled it
- Endosomal system genetics and autism spectrum disorders: A literature review.Neuroscience and biobehavioral reviews · 2016Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Integrative structural analysis of human endosomal NHE6 reveals a lipid-associated gate and disordered C-terminus.Nature communications · 2026Article
- Structure of NHE6 and its lipid-mediated interactions regulating endosomal pH.Nature communications · 2026Article
- Hypoxic glycolysis-driven histone lactylation activates NHE7 to promote endometrial cancer progression via COX6C-mediated endoplasmic reticulum stress.Apoptosis : an international journal on programmed cell death · 2026Article
- The Christianson syndrome protein, sodium hydrogen exchanger isoform 6, is required for fat accumulation.The Journal of physiology · 2025Article
- Alterations in the NaCerebellum (London, England) · 2025Article
- PIPNature communications · 2025Article
- Linking endo-lysosomal pH, sterol, and trafficking to neurodegenerative disease.FEMS yeast research · 2025Review
- Robust inhibitory glycinergic transmission and the effect of bafilomycin, folimycin and EIPA: lessons from the auditory brainstem.Frontiers in cellular neuroscience · 2025Article
- Review
- GGA1 interacts with the endosomal Na+/H+ exchanger NHE6 governing localization to the endosome compartment.The Journal of biological chemistry · 2024Article
- Potential for New Therapeutic Approaches by Targeting Lactate and pH Mediated Epigenetic Dysregulation in Major Mental Diseases.Biomedicines · 2024Review
- Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.Reviews of physiology, biochemistry and pharmacology · 2023Article
- Loss of endosomal exchanger NHE6 leads to pathological changes in tau in human neurons.Stem cell reports · 2022Article
- Phenotypic and genetic spectrum of ATP6V1A encephalopathy: a disorder of lysosomal homeostasis.Brain : a journal of neurology · 2022Article
- Genetic architecture and phenotypic landscape of deafness and onychodystrophy syndromes.Human genetics · 2022Review
- Article
- Donor Splice Site Variant inMedicina (Kaunas, Lithuania) · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Autism imposes a major impediment to childhood development and a huge emotional and financial burden on society. In recent years, there has been rapidly accumulating genetic evidence that links the eNHE, a subset of Na(+)/H(+) exchangers that localize to intracellular vesicles, to a variety of neurological conditions including autism, attention deficit hyperactivity disorder (ADHD), intellectual disability, and epilepsy. By providing a leak pathway for protons pumped by the V-ATPase, eNHE determine luminal pH and regulate cation (Na(+), K(+)) content in early and recycling endosomal compartments. Loss-of-function mutations in eNHE cause hyperacidification of endosomal lumen, as a result of imbalance in pump and leak pathways. Two isoforms, NHE6 and NHE9 are highly expressed in brain, including hippocampus and cortex. Here, we summarize evidence for the importance of luminal cation content and pH on processing, delivery and fate of cargo. Drawing upon insights from model organisms and mammalian cells we show how eNHE affect surface expression and function of membrane receptors and neurotransmitter transporters. These studies lead to cellular models of eNHE activity in pre- and post-synaptic neurons and astrocytes, where they could impact synapse development and plasticity. The study of eNHE has provided new insight on the mechanism of autism and other debilitating neurological disorders and opened up new possibilities for therapeutic intervention.
Indexed as
Identifiers
What OpenQuestion holds
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.