ArticleActa neuropathologica2017
Pathological TDP-43 changes in Betz cells differ from those in bulbar and spinal α-motoneurons in sporadic amyotrophic lateral sclerosis.
Article in Acta neuropathologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 107 citations in OpenAlex.
- Transcriptional targets of amyotrophic lateral sclerosis/frontotemporal dementia protein TDP-43 - meta-analysis and interactive graphical database.Disease models & mechanisms · 2022Pooled it
- Targeting TDP-43 in sporadic amyotrophic lateral sclerosis.Journal of neurology · 2026Review
- Axonal dying back of upper motor neurons in human ALS.Scientific reports · 2026Article
- TDP-43: [GU]-ardian of the transcriptome.Molecular neurodegeneration · 2026Review
- Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex.Nature communications · 2026Article
- Somatic gene mutations in the motor cortex of patients with sporadic amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Article
- Axonal dying back of upper motor neurons in human ALS.Research square · 2026Article
- Extracellular vesicles in TDP-43 proteinopathies: pathogenesis and biomarker potential.Molecular neurodegeneration · 2025Review
- Amyotrophic lateral sclerosis represents corticomotoneuronal system failure.Muscle & nerve · 2025Review
- Motor actions across psychiatric disorders: A research domain criteria (RDoC) perspective.Clinical psychology review · 2024Review
- Clinical spreading of muscle weakness in amyotrophic lateral sclerosis (ALS): a study in 910 patients.Journal of neurology · 2024Observational
- Neuropeptide FF (NPFF)-positive nerve cells of the human cerebral cortex and white matter in controls, selected neurodegenerative diseases, and schizophrenia.Acta neuropathologica communications · 2024Article
- History of ALS and the competing theories on pathogenesis: IFCN handbook chapter.Clinical neurophysiology practice · 2024Review
- Heterogeneous nuclear ribonucleoprotein D - an understudied subfamily affected in sporadic TDP-43 proteinopathies.Brain communications · 2024Article
- Betz cells of the primary motor cortex.The Journal of comparative neurology · 2024Review
- Loss of TDP-43 splicing repression occurs early in the aging population and is associated with Alzheimer's disease neuropathologic changes and cognitive decline.Acta neuropathologica · 2023Article
- Heterogeneity of cortical pTDP-43 inclusion morphologies in amyotrophic lateral sclerosis.Acta neuropathologica communications · 2023Article
- Corticospinal fibers with different origins impair in amyotrophic lateral sclerosis: A neurite orientation dispersion and density imaging study.CNS neuroscience & therapeutics · 2023Article
- TDP-43 differentially propagates to induce antero- and retrograde degeneration in the corticospinal circuits in mouse focal ALS models.Acta neuropathologica · 2023Article
- Survival in sporadic ALS is associated with lower p62 burden in the spinal cord.Journal of neuropathology and experimental neurology · 2023Article
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Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Two nerve cells types, Betz cells in layer Vb of the primary motor neocortex and α-motoneurons of the lower brainstem and spinal cord, become involved at the beginning of the pathological cascade underlying sporadic amyotrophic lateral sclerosis (sALS). In both neuronal types, the cell nuclei forfeit their normal (non-phosphorylated) expression of the 43-kDa transactive response DNA-binding protein (TDP-43). Here, we present initial evidence that in α-motoneurons the loss of normal nuclear TDP-43 expression is followed by the formation of phosphorylated TDP-43 aggregates (pTDP-43) within the cytoplasm, whereas in Betz cells, by contrast, the loss of normal nuclear TDP-43 expression remains mostly unaccompanied by the development of cytoplasmic aggregations. We discuss some implications of this phenomenon of nuclear clearing in the absence of cytoplasmic inclusions, namely, abnormal but soluble (and, thus, probably toxic) cytoplasmic TDP-43 could enter the axoplasm of Betz cells, and following its transmission to the corresponding α-motoneurons in the lower brainstem and spinal cord, possibly contribute in recipient neurons to the dysregulation of the normal nuclear protein. Because the cellular mechanisms that possibly inhibit the aggregation of TDP-43 in the cytoplasm of involved Betz cells are unknown, insight into such mechanisms could disclose a pathway by which the development of aggregates in this cell population could be accelerated, thereby opening an avenue for a causally based therapy.
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