ArticleNature neuroscience2025
Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson's disease.
Article in Nature neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Increased oxygen demand during exercise as a stimulus for neuroprotection: A working hypothesis.Neural regeneration research · 2026Article
- Small-molecule-induced neuron-specific hypoxia: recapitulating developmental angiogenesis for ischemic stroke therapy.Acta pharmacologica Sinica · 2026Article
- Smoking, Exhaled Carbon Monoxide, and Risk of Parkinson Disease.JAMA neurology · 2026Article
- Reduced microvascular coverage links a hypoxia-associated niche to microglial autophagic dysfunction in Parkinson's disease.Acta neuropathologica communications · 2026Article
- G-Quadruplexes: Structural Diversity and Emerging Roles in Biomolecular Condensation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Neuroprotective effects of ursodeoxycholic acid in Parkinson's disease and Alzheimer's disease.Neuroprotection (Chichester, England) · 2026Review
- Genetic and Proteomic Investigation of the Smoking-Parkinson's Disease Association.medRxiv : the preprint server for health sciences · 2026Article
- A hypoxia-sensitive medullary nucleus modulates cerebral blood flow via a disynaptic pathway to cortex.bioRxiv : the preprint server for biology · 2026Article
- Juggling Under Controlled Hypoxia as a Multimodal Coordinative and Cognitive Training in Parkinson's Disease-A Narrative Review.Journal of functional morphology and kinesiology · 2026Review
- Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mitochondrial resilience: a convergent framework for pathogenesis and neuroprotection in Parkinson's disease.Frontiers in pharmacology · 2026Review
- Vascular smooth muscle cell loss, but not neuroinflammation, drives cerebrovascular reactivity impairment in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Physiological Differences Underlying Divergent Hypoxia Responses and Altitude Adaptations in Humans, Rats and Mice.Comprehensive Physiology · 2025Review
- Hypoxia and Parkinson's Disease: A Dangerous Oversimplification Based on a Subpar Mouse Model.Nano LIFE · 2025Article
Corrections and comments
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Authors and funding
15 authors.
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Abstract
Parkinson's disease (PD) is characterized by inclusions of α-synuclein (α-syn) and mitochondrial dysfunction in dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). Patients with PD anecdotally experience symptom improvement at high altitude; chronic hypoxia prevents the development of Leigh-like brain disease in mice with mitochondrial complex I deficiency. Here we report that intrastriatal injection of α-syn preformed fibrils (PFFs) in mice resulted in neurodegeneration and movement disorder, which were prevented by continuous exposure to 11% oxygen. Specifically, PFF-induced α-syn aggregation resulted in brain tissue hyperoxia, lipid peroxidation and DA neurodegeneration in the SNpc of mice breathing 21% oxygen, but not in those breathing 11% oxygen. This neuroprotective effect of hypoxia was also observed in Caenorhabditis elegans. Moreover, initiating hypoxia 6 weeks after PFF injection reversed motor dysfunction and halted further DA neurodegeneration. These results suggest that hypoxia may have neuroprotective effects downstream of α-syn aggregation in PD, even after symptom onset and neuropathological changes.
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