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| DOI | Trouver le DOI : https://doi.org/10.1016/j.crneur.2023.100112 |
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| Auteur | Rechercher : Pileggi, Chantal A.1; Rechercher : Parmar, Gaganvir; Rechercher : Elkhatib, Hussein; Rechercher : Stewart, Corina M.; Rechercher : Alecu, Irina; Rechercher : Côté, Marceline; Rechercher : Bennett, Steffany A.L.; Rechercher : Sandhu, Jagdeep K.2; Rechercher : Cuperlovic-Culf, Miroslava1; Rechercher : Harper, Mary-EllenIdentifiant ORCID : https://orcid.org/0000-0003-3864-5886 |
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| Affiliation | - Conseil national de recherches du Canada. Technologies numériques
- Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Sujet | SARS-CoV-2; monoamine oxidase B; mitochondria; Parkinson’s disease |
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| Résumé | SARS-CoV-2 infection is associated with both acute and post-acute neurological symptoms. Emerging evidence suggests that SARS-CoV-2 can alter mitochondrial metabolism, suggesting that changes in brain metabolism may contribute to the development of acute and post-acute neurological complications. Monoamine oxidase B (MAOB) is a flavoenzyme located on the outer mitochondrial membrane that catalyzes the oxidative deamination of monoamine neurotransmitters. Computational analyses have revealed high similarity between the SARS-CoV-2 spike glycoprotein receptor binding domain on the ACE2 receptor and MAO-B, leading to the hypothesis that SARS-CoV-2 spike glycoprotein may alter neurotransmitter metabolism by interacting with MAO-B. Our results empirically establish that the SARS-CoV-2 spike glycoprotein interacts with MAO-B, leading to increased MAO-B activity in SH-SY5Y neuron-like cells. Common to neurodegenerative disease pathophysiological mechanisms, we also demonstrate that the spike glycoprotein impairs mitochondrial bioenergetics, induces oxidative stress, and perturbs the degradation of depolarized aberrant mitochondria through mitophagy. Our findings also demonstrate that SH-SY5Y neuron-like cells expressing the SARS-CoV-2 spike protein were more susceptible to MPTPinduced necrosis, likely necroptosis. Together, these results reveal novel mechanisms that may contribute to SARS-CoV-2-induced neurodegeneration. |
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| Date de publication | 2023-10-06 |
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| Maison d’édition | Elsevier |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 4f1e7867-048e-48bc-89b3-6f09615a66e2 |
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| Enregistrement créé | 2023-10-16 |
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| Enregistrement modifié | 2023-10-17 |
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