ArticleJournal of neurochemistry2018
A motor neuron strategy to save time and energy in neurodegeneration: adaptive protein stoichiometry.
Article in Journal of neurochemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Pooled it
- Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-TreatedInternational journal of molecular sciences · 2026Article
- SOD1, A Crucial Protein for Neural Biochemistry: Dysfunction and Risk of Amyotrophic Lateral Sclerosis.Molecular neurobiology · 2025Review
- Serum neurofilament light chain levels in myasthenia gravis patients with and without symptoms.Frontiers in medicine · 2025Article
- Emerging biomarkers in amyotrophic lateral sclerosis: from pathogenesis to clinical applications.Frontiers in molecular biosciences · 2025Review
- Advancing Clinical Use of Neurofilament Light Chain: Translational Insights From Research to Routine Practice.Biomarker insights · 2025Review
- CK and LRRK2 Involvement in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Neurofilament Isoform Promoter-Driven Expression of Therapeutic Genes.Translational vision science & technology · 2024Article
- Neurofilaments as biomarkers in neurological disorders - towards clinical application.Nature reviews. Neurology · 2024Review
- Studying serum neurofilament light chain levels as a potential new biomarker for small fiber neuropathy.European journal of neurology · 2024Article
- Biomarkers in amyotrophic lateral sclerosis: current status and future prospects.Nature reviews. Neurology · 2023Review
- The 2022 Lady Estelle Wolfson lectureship on neurofilaments.Journal of neurochemistry · 2022Review
- Blood biomarkers in ALS: challenges, applications and novel frontiers.Acta neurologica Scandinavica · 2022Review
- Intronic NEFH variant is associated with reduced risk for sporadic ALS and later age of disease onset.Scientific reports · 2022Article
- A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia.Brain : a journal of neurology · 2022Article
- Humoral response to neurofilaments and dipeptide repeats in ALS progression.Annals of clinical and translational neurology · 2021Article
- Neurofilament Proteins as Biomarkers to Monitor Neurological Diseases and the Efficacy of Therapies.Frontiers in neuroscience · 2021Review
- Blood neurofilament light: a critical review of its application to neurologic disease.Annals of clinical and translational neurology · 2020Review
- Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers.Molecular neurodegeneration · 2020Review
- Neurofilament Light Chain as a Biomarker, and Correlation with Magnetic Resonance Imaging in Diagnosis of CNS-Related Disorders.Molecular neurobiology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 6 countries.
Funding
Abstract
Neurofilament proteins (Nf) are a biomarker of disease progression in amyotrophic lateral sclerosis (ALS). This study investigated whether there are major differences in expression from in vivo measurements of neurofilament isoforms, from the light chain, NfL (68 kDa), compared with larger proteins, the medium chain (NfM, 150 kDa) and the heavy (NfH, 200-210 kDa) chains in ALS patients and healthy controls. New immunological methods were combined with Nf subunit stoichiometry calculations and Monte Carlo simulations of a coarse-grained Nf brush model. Based on a physiological Nf subunit stoichiometry of 7 : 3 : 2 (NfL:NfM:NfH), we found an 'adaptive' Nf subunit stoichiometry of 24 : 2.4 : 1.6 in ALS. Adaptive Nf stoichiometry preserved NfL gyration radius in the Nf brush model. The energy and time requirements for Nf translation were 56 ± 27k ATP (5.6 h) in control subjects compared to 123 ± 102k (12.3 h) in ALS with 'adaptive' (24:2.4:1.6) Nf stoichiometry (not significant) and increased significantly to 355 ± 330k (35.5 h) with 'luxury' (7:3:2) Nf subunit stoichiometry (p < 0.0001 for each comparison). Longitudinal disease progression-related energy consumption was highest with a 'luxury' (7:3:2) Nf stoichiometry. Therefore, an energy and time-saving option for motor neurons is to shift protein expression from larger to smaller (cheaper) subunits, at little or no costs on a protein structural level, to compensate for increased energy demands.
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Registered trials
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