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MINI-REVIEW

Hypoxia, sleep architecture, and brain clearance: Converging pathways in neurodegenerative disease

Josué Camberos-Barraza1 Karyme M. Alemán-Villa1 Alberto K. De la Herrán-Arita1*
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1 Department of Neuroscience, Faculty of Medicine, Autonomous University of Sinaloa, Culiacán, Sinaloa, Mexico
Received: 10 March 2026 | Revised: 11 June 2026 | Accepted: 16 June 2026 | Published online: 10 July 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Hypoxia is a fundamental biological stressor that profoundly alters neural function, sleep architecture, and metabolic homeostasis. Emerging evidence indicates that sleep is a critical regulator of glymphatic clearance, the perivascular cerebrospinal fluid exchange system responsible for removing metabolic waste products, such as amyloid-β and tau, from the brain. Disruption of oxygen homeostasis, whether acute, chronic, or intermittent, modifies sleep structure, alters astroglial physiology, and activates hypoxia-responsive signaling pathways that may impair glymphatic efficiency. This review synthesizes current knowledge on the bidirectional relationship between hypoxia and sleep, focusing on molecular mediators such as hypoxia-inducible factors, inflammatory cascades, oxidative stress, and aquaporin-4 polarization. We examine how hypoxia-induced sleep fragmentation and locus coeruleus-mediated noradrenergic arousal compromise brain clearance mechanisms, potentially accelerating neurodegenerative processes associated with Alzheimer’s disease and Parkinson’s disease. Clinical contexts such as obstructive sleep apnea, high-altitude exposure, and cardiopulmonary disorders are discussed as translational models of hypoxia-driven glymphatic dysfunction. Finally, we highlight therapeutic perspectives, including oxygen modulation strategies and pharmacologic manipulation of hypoxia signaling pathways. Understanding how hypoxia reshapes sleep-dependent clearance systems may reveal novel targets to mitigate neurodegenerative disease progression.

Keywords
Hypoxia
Sleep disruption
Neurodegenerative
Glymphatic dysfunction
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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