ReviewCurrent opinion in neurology2014
C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia: gain or loss of function?
Review in Current opinion in neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Stress granule formation helps to mitigate neurodegeneration.Nucleic acids research · 2024Article
- Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stress granule formation helps to mitigate neurodegeneration.bioRxiv : the preprint server for biology · 2023Article
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- Integrative genetic and single cell RNA sequencing analysis provides new clues to the amyotrophic lateral sclerosis neurodegeneration.Frontiers in neuroscience · 2023Article
- Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas.Journal of personalized medicine · 2022Review
- Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease.Frontiers in molecular neuroscience · 2022Review
- ModelingFrontiers in cellular neuroscience · 2021Review
- Emerging Mechanisms Underpinning Neurophysiological Impairments inFrontiers in cellular neuroscience · 2021Review
- Altered Phase Separation and Cellular Impact inFrontiers in cellular neuroscience · 2021Article
- Structural Features of Small Molecules Targeting the RNA Repeat Expansion That Causes Genetically Defined ALS/FTD.ACS chemical biology · 2020Article
- Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis.Cells · 2020Review
- From basic research to the clinic: innovative therapies for ALS and FTD in the pipeline.Molecular neurodegeneration · 2020Review
- Mutant C9orf72 human iPSC-derived astrocytes cause non-cell autonomous motor neuron pathophysiology.Glia · 2020Article
- Article
- SMN complex member Gemin3 self-interacts and has a functional relationship with ALS-linked proteins TDP-43, FUS and Sod1.Scientific reports · 2019Article
- C9orf72 Poly(PR) Dipeptide Repeats Disturb Biomolecular Phase Separation and Disrupt Nucleolar Function.Molecular cell · 2019Article
- The Hairpin Form of r(GCell chemical biology · 2019Article
- The Spectrum of Neurological and White Matter Changes and Premutation Status Categories of Older Male Carriers of theFrontiers in genetics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
purpose of reviewThe molecular mechanisms that underlie chromosome 9 open reading frame 72 (C9orf72)-associated amyotrophic lateral sclerosis and frontotemporal dementia are rapidly emerging. Two potential disease mechanisms have been postulated - gain or loss of function. We provide an overview of recent advances that support or oppose gain-of-function and loss-of-function mechanisms. RECENT
findingsSince the discovery that a noncoding repeat expansion in C9orf72 was responsible for chromosome 9-linked amyotrophic lateral sclerosis and frontotemporal dementia in 2011, a plethora of studies have investigated clinical, pathological and mechanistic aspects of the disease. Loss of function is supported by reduced levels of C9orf72 in patient brain and functional work, revealing a role of the C9orf72 protein in endocytic and autophagic pathways and motor function. Gain of function is supported by the presence in patient brain of both repeat RNA and protein aggregates. Repeat RNA aggregates termed RNA foci, a hallmark of noncoding repeat expansion diseases, have been shown to sequester proteins involved in RNA splicing, editing, nuclear export and nucleolar function. Repeat-associated non-ATG dependent translation gives rise to toxic dipeptide repeat proteins that form inclusions in patient tissue. Antisense oligonucleotides targeting C9orf72 have shown promise for combating gain-of-function toxicity. SUMMARY: Rapid progress is being made towards understanding this common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Overall, the weight of data currently sits in favour of gain of function as the most important disease mechanism, which has important implications for the development of effective and targeted therapies.
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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.