ArticleBrain : a journal of neurology2012
The mitochondrial calcium regulator cyclophilin D is an essential component of oestrogen-mediated neuroprotection in amyotrophic lateral sclerosis.
Article in Brain : a journal of neurology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis 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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Depression and obesity among females, are sex specificities considered?Archives of women's mental health · 2021Pooled it
- Propofol-Induced Mitochondrial Dysfunction Is Independent of Mitochondrial Permeability Transition.Biomedicines · 2025Article
- Sexual Dimorphism in Migraine. Focus on Mitochondria.Current pain and headache reports · 2025Review
- A Novel Retinal Nerve Fiber Layer Biomarker of Amyotrophic Lateral Sclerosis (ALS) Identified Using Longitudinal in vivo Ocular Imaging.Eye and brain · 2025Article
- Brain-body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis.Nature reviews. Neurology · 2024Review
- scAAV9-VEGF alleviates symptoms of amyotrophic lateral sclerosis (ALS) mice through regulating aromatase.Experimental brain research · 2023Article
- Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2023Review
- From mitochondria to sarcopenia: role of 17β-estradiol and testosterone.Frontiers in endocrinology · 2023Review
- Potential biological contributers to the sex difference in multiple sclerosis progression.Frontiers in immunology · 2023Article
- Characterizing Sex Differences in Mitochondrial Dysfunction After Severe Traumatic Brain Injury in Mice.Neurotrauma reports · 2023Article
- Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1Frontiers in cellular neuroscience · 2023Article
- Nanotherapeutics and the Brain.Annual review of chemical and biomolecular engineering · 2022Review
- Article
- Apoptosis in resistance arteries induced by hydrogen peroxide: greater resilience of endothelium versus smooth muscle.American journal of physiology. Heart and circulatory physiology · 2021Review
- Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia.FEBS open bio · 2021Article
- Sex differences in renal mitochondrial function: a hormone-gous opportunity for research.American journal of physiology. Renal physiology · 2020Review
- Cyclophilin D counterbalances mitochondrial calcium uniporter-mediated brain mitochondrial calcium uptake.Biochemical and biophysical research communications · 2020Article
- Sex differences in cancer mechanisms.Biology of sex differences · 2020Review
- Article
- Disease-directed engineering for physiology-driven treatment interventions in neurological disorders.APL bioengineering · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Amyotrophic lateral sclerosis is a devastating neurodegenerative disorder that is more prevalent in males than in females. A similar gender difference has been reported in some strains of transgenic mouse models of familial amyotrophic lateral sclerosis harbouring the G93A mutation in CuZn superoxide dismutase. Mitochondrial damage caused by pathological alterations in Ca(2+) accumulation is frequently involved in neurodegenerative diseases, including CuZn superoxide dismutase-related amyotrophic lateral sclerosis, but its association with gender is not firmly established. In this study, we examined the effects of genetic ablation of cyclophilin D on gender differences in mice expressing G93A mutant CuZn superoxide dismutase. Cyclophilin D is a mitochondrial protein that promotes mitochondrial damage from accumulated Ca(2+). As anticipated, we found that cyclophilin D ablation markedly increased Ca(2+) retention in brain mitochondria of both males and females. Surprisingly, cyclophilin D ablation completely abolished the phenotypic advantage of G93A females, with no effect on disease in males. We also found that the 17β-oestradiol decreased Ca(2+) retention in brain mitochondria, and that cyclophilin D ablation abolished this effect. Furthermore, 17β-oestradiol protected G93A cortical neurons and spinal cord motor neurons against glutamate toxicity, but the protection was lost in neurons lacking cyclophilin D. Taken together, these results identify a novel mechanism of oestrogen-mediated neuroprotection in CuZn superoxide dismutase-related amyotrophic lateral sclerosis, whereby Ca(2+) overload and mitochondrial damage are prevented in a cyclophilin D-dependent manner. Such a protective mechanism may contribute to the lower incidence and later onset of amyotrophic lateral sclerosis, and perhaps other chronic neurodegenerative diseases, in females.
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.