ArticleThe Journal of biological chemistry2012
α-Synuclein induces alterations in adult neurogenesis in Parkinson disease models via p53-mediated repression of Notch1.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 75 citations in OpenAlex.
- Review
- Deciphering the microenvironment of adult neurogenesis: a perspective from neurodegenerative diseases.Translational neurodegeneration · 2026Review
- Neural stem cells of the subventricular zone: A potential stem cell pool for brain repair in Parkinson's disease.Stem cell reports · 2025Review
- Unraveling Dysregulated Cell Signaling Pathways, Genetic and Epigenetic Mysteries of Parkinson's Disease.Molecular neurobiology · 2024Review
- Nuclear alpha-synuclein accelerates cell senescence and neurodegeneration.Immunity & ageing : I & A · 2024Article
- Pathological and physiological functional cross-talks of α-synuclein and tau in the central nervous system.Neural regeneration research · 2024Review
- The Common Denominators of Parkinson's Disease Pathogenesis and Methamphetamine Abuse.Current neuropharmacology · 2024Review
- Article
- Neuromodulation in Parkinson's disease targeting opioid and cannabinoid receptors, understanding the role of NLRP3 pathway: a novel therapeutic approach.Inflammopharmacology · 2023Review
- Unraveling the Complex Interplay between Alpha-Synuclein and Epigenetic Modification.International journal of molecular sciences · 2023Review
- Thymoquinone Improved Nonylphenol-Induced Memory Deficit and Neurotoxicity Through Its Antioxidant and Neuroprotective Effects.Molecular neurobiology · 2022Article
- Association of p53 with Neurodegeneration in Parkinson's Disease.Parkinson's disease · 2022Review
- Neural Stem Cells: What Happens When They Go Viral?Viruses · 2021Review
- Review
- View Point: Disease Modification and Cell Secretome Based Approaches in Parkinson's Disease: Are We on the Right Track?Biologics : targets & therapy · 2021Review
- Effects of Alpha-Synuclein Targeted Antisense Oligonucleotides on Lewy Body-Like Pathology and Behavioral Disturbances Induced by Injections of Pre-Formed Fibrils in the Mouse Motor Cortex.Journal of Parkinson's disease · 2021Article
- The Role of Alpha-Synuclein and Other Parkinson's Genes in Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2020Review
- Parkinson's disease, aging and adult neurogenesis: Wnt/β-catenin signalling as the key to unlock the mystery of endogenous brain repair.Aging cell · 2020Review
- Regeneration ThroughFrontiers in cellular neuroscience · 2020Review
- Dual Effects of Human Placenta-Derived Neural Cells on Neuroprotection and the Inhibition of Neuroinflammation in a Rodent Model of Parkinson's Disease.Cell transplantation · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Parkinson disease is characterized by the loss of dopaminergic neurons mainly in the substantia nigra. Accumulation of α-synuclein and cell loss has been also reported in many other brain regions including the hippocampus, where it might impair adult neurogenesis, contributing to nonmotor symptoms. However, the molecular mechanisms of these alterations are still unknown. In this report we show that α-synuclein-accumulating adult rat hippocampus neural progenitors present aberrant neuronal differentiation, with reduction of Notch1 expression and downstream signaling targets. We characterized a Notch1 proximal promoter that contains p53 canonical response elements. In vivo binding of p53 represses the transcription of Notch1 in neurons. Moreover, we demonstrated that α-synuclein directly binds to the DNA at Notch1 promoter vicinity and also interacts with p53 protein, facilitating or increasing Notch1 signaling repression, which interferes with maturation and survival of neural progenitors cells. This study provides a molecular basis for α-synuclein-mediated disruption of adult neurogenesis in Parkinson disease.
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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.