ArticleNeurobiology of aging2020
Apoptosis signal regulating kinase 1 deletion mitigates α-synuclein pre-formed fibril propagation in mice.
Article in Neurobiology of aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 2 of them syntheses that pooled it.
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Who cites it
9 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Do Naturally Occurring Antioxidants Protect Against Neurodegeneration of the Dopaminergic System? A Systematic Revision in Animal Models of Parkinson's Disease.Current neuropharmacology · 2022Pooled it
- Clinical potential and current progress of mesenchymal stem cells for Parkinson's disease: a systematic review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Pooled it
- α-synuclein in Parkinson's disease: a central point of convergence with depression.NPJ Parkinson's disease · 2025Review
- Targeting ASK1 signaling in neurodegeneration: molecular insights and therapeutic promise.Apoptosis : an international journal on programmed cell death · 2025Review
- Protein kinases in neurodegenerative diseases: current understandings and implications for drug discovery.Signal transduction and targeted therapy · 2025Review
- Auto-loaded TRAIL-exosomes derived from induced neural stem cells for brain cancer therapy.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Transcriptional mutagenesis of α-synuclein caused by DNA oxidation in Parkinson's disease pathogenesis.Acta neuropathologica · 2023Article
- Intrinsic disorder in proteins associated with oxidative stress-induced JNK signaling.Cellular and molecular life sciences : CMLS · 2022Article
- MicroRNA-7 Protects Against Neurodegeneration Induced by α-Synuclein Preformed Fibrils in the Mouse Brain.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
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Authors and funding
10 authors.
Funding
Abstract
α-Synuclein (α-Syn) is a key pathogenic protein in α-synucleinopathies including Parkinson disease and dementia with Lewy bodies. Accumulating evidence has shown that misfolded fibrillar α-Syn is transmitted from cell-to-cell, a phenomenon that correlates with clinical progression of the disease. We previously showed that deleting the MAP3 kinase apoptosis signal-regulating kinase 1 (ASK1), which is a central player linking oxidative stress with neuroinflammation, mitigates the phenotype of α-Syn transgenic mice. However, whether ASK1 impacts pathology and disease progression induced by recombinant α-Syn pre-formed fibrils (PFF) remains unknown. Here, we compared the neuropathological and behavioral phenotype of ASK1 knock-out mice with that of wild-type mice following intrastriatal injections of α-Syn PFF. At 6 months post-injections, ASK1 null mice exhibited reduced amount of phosphorylated α-Syn aggregates in the striatum and cortex, and less pronounced degeneration of the nigrostriatal pathway. Additionally, the neuroinflammatory reaction to α-Syn PFF injection and propagation seen in wild-type mice was attenuated in ASK1 knock-out animals. These neuropathological markers were associated with better behavioral performance. These data suggest that ASK1 plays an important role in pathological α-Syn fibril transmission and, consequently, may impact disease progression. These findings collectively support inhibiting ASK1 as a disease modifying therapeutic strategy for Parkinson disease and related α-synucleinopathies.
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