ArticleMolecular neurodegeneration2011
Dopamine and α-synuclein dysfunction in Smad3 null mice.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 65 citations in OpenAlex.
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- Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases.Biomedicines · 2024Review
- HIPK2 in the physiology of nervous system and its implications in neurological disorders.Biochimica et biophysica acta. Molecular cell research · 2023Review
- Inferring the Effects of Protein Variants on Protein-Protein Interactions with Interpretable Transformer Representations.Research (Washington, D.C.) · 2023Article
- TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications.Biomedicines · 2022Review
- Developmental pathways linked to the vulnerability of adult midbrain dopaminergic neurons to neurodegeneration.Frontiers in molecular neuroscience · 2022Review
- The Twofold Role of Osteogenic Small Molecules in Parkinson's Disease Therapeutics: Crosstalk of Osteogenesis and Neurogenesis.BioMed research international · 2022Review
- Review
- Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson's disease and roles of microglia, proinflammatory factors, and MAPK.Journal of neuroinflammation · 2020Article
- TGF-β/Smad3 Signalling Modulates GABA Neurotransmission: Implications in Parkinson's Disease.International journal of molecular sciences · 2020Review
- Loss of SATB1 Induces p21-Dependent Cellular Senescence in Post-mitotic Dopaminergic Neurons.Cell stem cell · 2019Article
- CDKL5 deficiency predisposes neurons to cell death through the deregulation of SMAD3 signaling.Brain pathology (Zurich, Switzerland) · 2019Article
- Deficiency in Neuronal TGF-β Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-β Signaling Protects against MPTP Neurotoxicity in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- KLK6 proteolysis is implicated in the turnover and uptake of extracellular alpha-synuclein species.Oncotarget · 2017Article
- Dopaminergic Neurons and Brain Reward Pathways: From Neurogenesis to Circuit Assembly.The American journal of pathology · 2016Review
- p38 MAPK and PI3K/AKT Signalling Cascades inParkinson's Disease.International journal of molecular and cellular medicine · 2015Review
- How to make striatal projection neurons.Neurogenesis (Austin, Tex.) · 2015Review
- Models of α-synuclein aggregation in Parkinson's disease.Acta neuropathologica communications · 2014Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundParkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra (SN). Transforming growth factor-β1 (TGF-β1) levels increase in patients with PD, although the effects of this increment remain unclear. We have examined the mesostriatal system in adult mice deficient in Smad3, a molecule involved in the intracellular TGF-β1 signalling cascade.
resultsStriatal monoamine oxidase (MAO)-mediated dopamine (DA) catabolism to 3,4-dihydroxyphenylacetic acid (DOPAC) is strongly increased, promoting oxidative stress that is reflected by an increase in glutathione levels. Fewer astrocytes are detected in the ventral midbrain (VM) and striatal matrix, suggesting decreased trophic support to dopaminergic neurons. The SN of these mice has dopaminergic neuronal degeneration in its rostral portion, and the pro-survival Erk1/2 signalling is diminished in nigra dopaminergic neurons, not associated with alterations to p-JNK or p-p38. Furthermore, inclusions of α-synuclein are evident in selected brain areas, both in the perikaryon (SN and paralemniscal nucleus) or neurites (motor and cingulate cortices, striatum and spinal cord). Interestingly, these α-synuclein deposits are detected with ubiquitin and P(S129)-α-synuclein in a core/halo cellular distribution, which resemble those observed in human Lewy bodies (LB).
conclusionsSmad3 deficiency promotes strong catabolism of DA in the striatum (ST), decrease trophic and astrocytic support to dopaminergic neurons and may induce α-synuclein aggregation, which may be related to early parkinsonism. These data underline a role for Smad3 in α-synuclein and DA homeostasis, and suggest that modulatory molecules of this signalling pathway should be evaluated as possible neuroprotective agents.
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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.