ReviewBrain research2018
Synaptic dysfunction and altered excitability in C9ORF72 ALS/FTD.
Review in Brain research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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.
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
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Elucidating the Role of Cerebellar Synaptic Dysfunction in C9orf72-ALS/FTD - a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2022Pooled it
- A Systematic Review of Common and Brain-Disease-Specific RNA Editing Alterations Providing Novel Insights into Neurological and Neurodegenerative Disease Manifestations.Biomolecules · 2022Pooled it
- Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.Biogerontology · 2026Review
- Synaptic changes contribute to persistent extra-motor behaviour deficits in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- An organ-chip model of sporadic ALS using iPSC-derived spinal cord motor neurons and an integrated blood-brain-like barrier.Cell stem cell · 2025Article
- Loss of intracellular ATP affects axoplasmic viscosity and pathological protein aggregation in mammalian neurons.Science advances · 2025Article
- Disparate and shared transcriptomic signatures associated with cortical atrophy in genetic behavioral variant frontotemporal degeneration.Molecular neurodegeneration · 2025Article
- A Survey on Computational Methods in Drug Discovery for Neurodegenerative Diseases.Biomolecules · 2024Review
- Molecular pathology, developmental changes and synaptic dysfunction in (pre-) symptomatic human C9ORF72-ALS/FTD cerebral organoids.Acta neuropathologica communications · 2024Article
- Poly-GR repeats associated with ALS/FTD geneScience signaling · 2024Article
- Review
- ICA-27243 improves neuromuscular function and preserves motoneurons in the transgenic SOD1Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.Frontiers in molecular neuroscience · 2024Review
- Deciphering the interactome of Ataxin-2 and TDP-43 in iPSC-derived neurons for potential ALS targets.PloS one · 2024Article
- Repeated mild traumatic brain injury triggers pathology in asymptomatic C9ORF72 transgenic mice.Brain : a journal of neurology · 2023Article
- Article
- Article
- Dorsomedial prefrontal hypoexcitability underlies lost empathy in frontotemporal dementia.Neuron · 2023Article
- Current insights in the molecular genetic pathogenesis of amyotrophic lateral sclerosis.Frontiers in neuroscience · 2023Review
- Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex.Acta neuropathologica communications · 2022Article
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
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis. The most common shared genetic mutation in ALS/FTD is a hexanucleuotide repeat expansion within intron 1 of C9ORF72 (C9). Three potentially overlapping, putative toxic mechanisms have been proposed: loss of function due to haploinsufficient expression of the C9ORF72 mRNA, gain of function of the repeat RNA aggregates, or RNA foci, and repeat-associated non-ATG-initiated translation (RAN) of the repeat RNA into toxic dipeptide repeats (DPRs). Regardless of the causative mechanism, disease symptoms are ultimately caused by a failure of neurotransmission in three regions: the brain, the spinal cord, and the neuromuscular junction. Here, we review C9 ALS/FTD-associated synaptic dysfunction and aberrant neuronal excitability in these three key regions, focusing on changes in morphology and synapse formation, excitability, and excitotoxicity in patients, animal models, and in vitro models. We compare these deficits to those seen in other forms of ALS and FTD in search of shared pathways, and discuss the potential targeting of synaptic dysfunctions for therapeutic intervention in ALS and FTD patients.
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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.