ReviewActa neuropathologica2012
Mechanisms of disease in frontotemporal lobar degeneration: gain of function versus loss of function effects.
Review in Acta neuropathologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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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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
52 citing papers in PubMed, 107 citations in OpenAlex.
- Chemical and Molecular Strategies in Restoring Autophagic Flux in TDP-43 Proteinopathy.Molecules (Basel, Switzerland) · 2026Review
- Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.bioRxiv : the preprint server for biology · 2025Article
- Detection of an Intermediate in the Unfolding Process of the N-Terminal Domain of TDP-43.ACS omega · 2025Article
- Co-Aggregation of TDP-43 with Other Pathogenic Proteins and Their Co-Pathologies in Neurodegenerative Diseases.International journal of molecular sciences · 2024Review
- Review
- Biophysical characterization of the phase separation of TDP-43 devoid of the C-terminal domain.Cellular & molecular biology letters · 2024Article
- Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia.American journal of human genetics · 2024Article
- Mis-spliced transcripts generate de novo proteins in TDP-43-related ALS/FTD.Science translational medicine · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- AnAnnals of medicine · 2023Article
- RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.eLife · 2023Article
- TDP-43 pathology in Drosophila induces glial-cell type specific toxicity that can be ameliorated by knock-down of SF2/SRSF1.PLoS genetics · 2023Article
- TDP-43 pathology inbioRxiv : the preprint server for biology · 2023Article
- Mis-spliced transcripts generatebioRxiv : the preprint server for biology · 2023Article
- Neuronal overexpression of hTDP-43 inmicroPublication biology · 2023Article
- Biophysical characterization of full-length TAR DNA-binding protein (TDP-43) phase separation.Protein science : a publication of the Protein Society · 2022Article
- Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD.International journal of molecular sciences · 2022Review
- A quantitative biology approach correlates neuronal toxicity with the largest inclusions of TDP-43.Science advances · 2022Article
- Low-level overexpression of wild type TDP-43 causes late-onset, progressive neurodegeneration and paralysis in mice.PloS one · 2022Article
- Neuroglial Senescence, α-Synucleinopathy, and the Therapeutic Potential of Senolytics in Parkinson's Disease.Frontiers in neuroscience · 2022Review
Corrections and comments
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Authors and funding
6 authors at 6 institutions in 5 countries.
Funding
Abstract
Frontotemporal lobar degeneration (FTLD) is clinically, pathologically and genetically heterogeneous. Three major proteins are implicated in its pathogenesis. About half of cases are characterized by depositions of the microtubule associated protein, tau (FTLD-tau). In most of the remaining cases, deposits of the transactive response (TAR) DNA-binding protein with Mw of 43 kDa, known as TDP-43 (FTLD-TDP), are seen. Lastly, about 5-10 % of cases are characterized by abnormal accumulations of a third protein, fused in sarcoma (FTLD-FUS). Depending on the protein concerned, the signature accumulations can take the form of inclusion bodies (neuronal cytoplasmic inclusions and neuronal intranuclear inclusions) or dystrophic neurites, in the cerebral cortex, hippocampus and subcortex. In some instances, glial cells are also affected by inclusion body formation. In motor neurone disease (MND), TDP-43 or FUS inclusions can present within motor neurons of the brain stem and spinal cord. This present paper attempts to critically examine the role of such proteins in the pathogenesis of FTLD and MND as to whether they might exert a direct pathogenetic effect (gain of function), or simply act as relatively innocent witnesses to a more fundamental loss of function effect. We conclude that although there is strong evidence for both gain and loss of function effects in respect of each of the proteins concerned, in reality, it is likely that each is a single face of either side of the coin, and that both will play separate, though complementary, roles in driving the damage which ultimately leads to the downfall of neurons and clinical expression of disease.
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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.