ArticleCell death and differentiation2013
Acidotoxicity and acid-sensing ion channels contribute to motoneuron degeneration.
Article in Cell death and differentiation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 9 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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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Article
- Amide signal intensities may be reduced in the motor cortex and the corticospinal tract of ALS patients.European radiology · 2021Article
- Altered Expression Pattern of Acid-Sensing Ion Channel Isoforms in Piriform Cortex After Seizures.Molecular neurobiology · 2016Article
- AMPK Signalling and Defective Energy Metabolism in Amyotrophic Lateral Sclerosis.Neurochemical research · 2016Review
- Acid-sensing ion channels: potential therapeutic targets for neurologic diseases.Translational neurodegeneration · 2015Article
- Potential involvement of intracellular pH in a mouse model of amyotrophic lateral sclerosis.Amyotrophic lateral sclerosis & frontotemporal degeneration · 2014Article
- Intracellular ASIC1a regulates mitochondrial permeability transition-dependent neuronal death.Cell death and differentiation · 2013Article
- Metabolic signatures of amyotrophic lateral sclerosis reveal insights into disease pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Conformational changes in the lower palm domain of ASIC1a contribute to desensitization and RFamide modulation.PloS one · 2013Article
Corrections and comments
- Retraction · 2014-02-21Error in Data · Error in Image · Falsification/Fabrication of Image · Investigation by Journal/Publisher · Objections by Third Party ·
- Retracted
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition with no cure. Mitochondrial dysfunction, Ca(2+) overloading and local hypoxic/ischemic environments have been implicated in the pathophysiology of ALS and are conditions that may initiate metabolic acidosis in the affected tissue. We tested the hypothesis that acidotoxicity and acid-sensing ion channels (ASICs) are involved in the pathophysiology of ALS. We found that motoneurons were selectively vulnerable to acidotoxicity in vitro, and that acidotoxicity was partially reduced in asic1a-deficient motoneuron cultures. Cross-breeding of SOD1(G93A) ALS mice with asic1a-deficient mice delayed the onset and progression of motor dysfunction in SOD1 mice. Interestingly, we also noted a strong increase in ASIC2 expression in motoneurons of SOD1 mice and sporadic ALS patients during disease progression. Pharmacological pan-inhibition of ASIC channels with the lipophilic amiloride derivative, 5-(N,N-dimethyl)-amiloride hydrochloride, potently protected cultured motoneurons against acidotoxicity, and, given post-symptom onset, significantly improved lifespan, motor performance and motoneuron survival in SOD1 mice. Together, our data provide strong evidence for the involvement of acidotoxicity and ASIC channels in motoneuron degeneration, and highlight the potential of ASIC inhibitors as a new treatment approach for ALS.
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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.