ArticleCell death & disease2019
Ablation of RIP3 protects from dopaminergic neurodegeneration in experimental Parkinson's disease.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Caspase-8 in inflammatory diseases: a potential therapeutic target.Cellular & molecular biology letters · 2024Review
- Dopaminergic neurons lacking Caspase-3 avoid apoptosis but undergo necrosis after MPTP treatment inducing a Galectin-3-dependent selective microglial phagocytic response.Cell death & disease · 2024Article
- The necroptosis cell death pathway drives neurodegeneration in Alzheimer's disease.Acta neuropathologica · 2024Review
- Article
- RIP3 in Necroptosis: Underlying Contributions to Traumatic Brain Injury.Neurochemical research · 2024Review
- Microglial cGAS drives neuroinflammation in the MPTP mouse models of Parkinson's disease.CNS neuroscience & therapeutics · 2023Article
- Outcomes of RIP Kinase Signaling During Neuroinvasive Viral Infection.Current topics in microbiology and immunology · 2023Review
- Tetrahydrobiopterin in Cell Function and Death Mechanisms.Antioxidants & redox signaling · 2022Review
- Supramolecular organizing centers at the interface of inflammation and neurodegeneration.Frontiers in immunology · 2022Review
- RIP3 Contributes to Cardiac Hypertrophy by Influencing MLKL-Mediated Calcium Influx.Oxidative medicine and cellular longevity · 2022Article
- Necroptosis in CNS diseases: Focus on astrocytes.Frontiers in aging neuroscience · 2022Review
- Parkinson's disease and microRNAs - Lessons from model organisms and human studies.Experimental gerontology · 2021Review
- Preclinical Evidence for the Interplay between Oxidative Stress and RIP1-Dependent Cell Death in Neurodegeneration: State of the Art and Possible Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2021Review
- Inhibition of neuronal necroptosis mediated by RIP1/RIP3/MLKL provides neuroprotective effects on kaolin-induced hydrocephalus in mice.Cell proliferation · 2021Article
- Fibrillar α-synuclein induces neurotoxic astrocyte activation via RIP kinase signaling and NF-κB.Cell death & disease · 2021Article
- Discovery of a Necroptosis Inhibitor Improving Dopaminergic Neuronal Loss after MPTP Exposure in Mice.International journal of molecular sciences · 2021Article
- Ubiquitin signalling in neurodegeneration: mechanisms and therapeutic opportunities.Cell death and differentiation · 2021Review
- miR-335 Targets LRRK2 and Mitigates Inflammation in Parkinson's Disease.Frontiers in cell and developmental biology · 2021Article
- Dietary Antioxidants and Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is driven by dopaminergic neurodegeneration in the substantia nigra pars compacta (SN) and striatum. Although apoptosis is considered the main neurodegenerative mechanism, other cell death pathways may be involved. In this regard, necroptosis is a regulated form of cell death dependent on receptor interacting protein 3 (RIP3), a protein also implicated in apoptosis and inflammation independently of its pro-necroptotic activity. Here, we explored the role of RIP3 genetic deletion in in vivo and in vitro PD models. Firstly, wild-type (Wt) and RIP3 knockout (RIP3ko) mice were injected intraperitoneally with MPTP (40 mg/kg, i.p.), and sacrificed after either 6 or 30 days. RIP3ko protected from dopaminergic neurodegeneration in the SN of MPTP-injected mice, but this effect was independent of necroptosis. In keeping with this, necrostatin-1s (10 mg/kg/day, i.p.) did not afford full neuroprotection. Moreover, MPTP led to DNA fragmentation, caspase-3 activation, lipid peroxidation and BAX expression in Wt mice, in the absence of caspase-8 cleavage, suggesting intrinsic apoptosis. This was mimicked in primary cortical neuronal cultures exposed to the active MPTP metabolite. RIP3 deficiency in cultured cells and in mouse brain abrogated all phenotypes. Curiously, astrogliosis was increased in the striatum of MPTP-injected Wt mice and further exacerbated in RIP3ko mice. This was accompanied by absence of microgliosis and reposition of glial cell line-derived neurotrophic factor (GDNF) levels in the striata of MPTP-injected RIP3ko mice when compared to MPTP-injected Wt mice, which in turn showed a massive GDNF decrease. RIP3ko primary mixed glial cultures also presented decreased expression of inflammation-related genes upon inflammatory stimulation. These findings hint at possible undescribed non-necroptotic roles for RIP3 in inflammation and MPTP-driven cell death, which can contribute to PD progression.
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