ArticleCell death & disease2014
Heme oxygenase-1 protects against Alzheimer's amyloid-β(1-42)-induced toxicity via carbon monoxide production.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 92 citations in OpenAlex.
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- Mid-life exposure to chronic stress accelerates cerebrovascular dysfunction and upregulates oxidative stress in Alzheimer's disease mice.Journal of Alzheimer's disease : JAD · 2025Article
- Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Curcumin ameliorates cerulein‑induced chronic pancreatitis through Nrf‑2/HO‑1 signaling.Molecular medicine reports · 2025Article
- Iron Overload, Microbleeding and the Role of Bilirubin in Alzheimer's Disease Brain: Revisiting the Vascular Hypothesis.International journal of molecular sciences · 2025Review
- The Role of Oligodendrocyte Lineage Cells in the Pathogenesis of Alzheimer's Disease.Neurochemical research · 2025Review
- The Neural Palette of Heme: Altered Heme Homeostasis Underlies Defective Neurotransmission, Increased Oxidative Stress, and Disease Pathogenesis.Antioxidants (Basel, Switzerland) · 2024Review
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- Ginsenosides Rg1 and Rg2 Activate Autophagy and Attenuate Oxidative Stress in Neuroblastoma Cells Overexpressing Aβ(1-42).Antioxidants (Basel, Switzerland) · 2024Article
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- Clearing the Smoke: What Protects Smokers from Parkinson's Disease?Movement disorders : official journal of the Movement Disorder Society · 2024Review
- Heme catabolism and heme oxygenase-1-expressing myeloid cells in pathophysiology.Frontiers in immunology · 2024Review
- Targeting Ferroptosis: A Novel Strategy for the Treatment of Atherosclerosis.Mini reviews in medicinal chemistry · 2024Review
- Dimethyl Fumarate as Potential Treatment for Alzheimer's Disease: Rationale and Clinical Trial Design.Biomedicines · 2023Review
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- The Role of Gasotransmitter-Dependent Signaling Mechanisms in Apoptotic Cell Death in Cardiovascular, Rheumatic, Kidney, and Neurodegenerative Diseases and Mental Disorders.International journal of molecular sciences · 2023Review
- Cellular Stress Response (Hormesis) in Response to Bioactive Nutraceuticals with Relevance to Alzheimer Disease.Antioxidants & redox signaling · 2023Review
- A glance through the effects of CD4Computational and structural biotechnology journal · 2023Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Since apoptosis contributes to the neuronal loss associated with amyloid β peptide (Aβ) toxicity in AD, we investigated the protective effects of HO-1 and CO against Aβ(1-42) toxicity in SH-SY5Y cells, employing cells stably transfected with empty vector or expressing the cellular prion protein, PrP(c), and rat primary hippocampal neurons. Aβ(1-42) (containing protofibrils) caused a concentration-dependent decrease in cell viability, attributable at least in part to induction of apoptosis, with the PrP(c)-expressing cells showing greater susceptibility to Aβ(1-42) toxicity. Pharmacological induction or genetic over-expression of HO-1 significantly ameliorated the effects of Aβ(1-42). The CO-donor CORM-2 protected cells against Aβ(1-42) toxicity in a concentration-dependent manner. Electrophysiological studies revealed no differences in the outward current pre- and post-Aβ(1-42) treatment suggesting that K+ channel activity is unaffected in these cells. Instead, Aβ toxicity was reduced by the L-type Ca2+ channel blocker nifedipine, and by the CaMKKII inhibitor, STO-609. Aβ also activated the downstream kinase, AMP-dependent protein kinase (AMPK). CO prevented this activation of AMPK. Our findings indicate that HO-1 protects against Aβ toxicity via production of CO. Protection does not arise from inhibition of apoptosis-associated K+ efflux, but rather by inhibition of AMPK activation, which has been recently implicated in the toxic effects of Aβ. These data provide a novel, beneficial effect of CO which adds to its growing potential as a therapeutic agent.
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Registered trials
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