ArticleMolecular neurobiology2021
Treadmill Exercise Alleviates Brain Iron Dyshomeostasis Accelerating Neuronal Amyloid-β Production, Neuronal Cell Death, and Cognitive Impairment in Transgenic Mice Model of Alzheimer's Disease.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 46 citations in OpenAlex.
- Effects of aerobic exercise on cognitive function in older adults with mild cognitive impairment: a systematic review and meta-analysis.Frontiers in psychiatry · 2025Pooled it
- Exercise Training for Mild Cognitive Impairment Adults Older Than 60: A Systematic Review and Meta-Analysis.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Pseudohypoxia induced by iron chelators preserves working memory performance in aged mice.Scientific reports · 2026Article
- Potential Mechanisms of Exercise-Mediated Ferroptosis Regulation in Central Nervous System Diseases.Molecular neurobiology · 2025Review
- TLR1-Regulated Ferroptosis Gene Decreases the Occurrence of Restless Legs Syndrome.Brain and behavior · 2025Article
- The Potential Regulators of Amyloidogenic Pathway of APP Processing in Alzheimer's Disease.Biomedicines · 2025Review
- Amyloid-beta metabolism in age-related neurocardiovascular diseases.European heart journal · 2025Review
- Exercise mitigates Alzheimer's disease by targeting ferroptosis driven by cellular senescence.Frontiers in cell and developmental biology · 2025Review
- Exercise as a Therapeutic Intervention for Alzheimer's Disease.Advances in neurobiology · 2025Review
- Targeting necroptosis in Alzheimer's disease: can exercise modulate neuronal death?Frontiers in aging neuroscience · 2025Review
- Ferroptosis in neurodegenerative diseases: potential mechanisms of exercise intervention.Frontiers in cell and developmental biology · 2025Review
- Distinct regional vulnerability to Aβ and iron accumulation in post mortem AD brains.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Plasma proteomic biomarkers and the association between poor cardiovascular health and incident dementia: The UK Biobank study.Brain, behavior, and immunity · 2024Article
- Brain Iron Dyshomeostasis and Ferroptosis in Alzheimer's Disease Pathophysiology: Two Faces of the Same Coin.Aging and disease · 2024Review
- Exercise therapy of mild cognitive impairment: EEG could enhance efficiency.Frontiers in aging neuroscience · 2024Article
- 8-weeks aerobic exercise ameliorates cognitive deficit and mitigates ferroptosis triggered by iron overload in the prefrontal cortex ofFrontiers in neuroscience · 2024Article
- Analysis of Effect of Intensity of Aerobic Exercise on Cognitive and Motor Functions and Neurotrophic Factor Expression Patterns in an Alzheimer's Disease Rat Model.Journal of personalized medicine · 2023Article
- Brain metabolism in Alzheimer's disease: biological mechanisms of exercise.Translational neurodegeneration · 2023Review
- Brain Iron Metabolism, Redox Balance and Neurological Diseases.Antioxidants (Basel, Switzerland) · 2023Review
- Revisiting the effects of exercise on cerebral neurovascular functions in rats using multimodal assessment techniques.iScience · 2023Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Brain iron increases with age and abnormal brain iron metabolism is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD). The iron-regulatory effect of furin, a ubiquitously expressed proconvertase, might play an important role in AD. Therefore, there is an urgent need to study the effect of furin on iron regulation in AD. For that purpose, we aimed to determine the role of physical exercise in AD associated with brain iron dyshomeostasis. Treadmill exercise attenuated the AD-related abnormal brain iron regulation by furin in vivo, as demonstrated via experiments in aged APP-C105 mice. Next, we examined whether treadmill exercise decreases excessive iron, directly affecting amyloid-β (Aβ) production through the regulation of α-secretase-dependent processing of amyloid protein precursor (APP) involved in the modulation of furin activity. We first observed that cognitive decline and Aβ-induced neuronal cell death were induced by disruption of APP processing via excess iron-induced disruption of furin activity in aged APP-C105 mice. The induced cognitive decline and cell death were attenuated by treadmill exercise. This result suggests that treadmill exercise alleviated cognitive decline and Aβ-induced neuronal cell death by promoting α-secretase-dependent processing of APP through low iron-induced enhancement of furin activity. This is concomitant with decreasing levels of lipid peroxidation products and promoting antioxidant defense enzyme capacities. Therefore, iron-targeted therapeutic strategies involving treadmill exercise might be useful for patients with AD.
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