ArticleAging cell2022
Reducing ER stress with chaperone therapy reverses sleep fragmentation and cognitive decline in aged mice.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- The role of sleep stages in the regulation of erectile function: impacts of REM sleep fragmentation.International journal of impotence research · 2026Review
- The unfolded protein response in progeria arteries originates from non-endothelial cell types.Life science alliance · 2026Article
- Expression and role of HSPA5 in environmental toxin-induced neurological disorders.Frontiers in molecular neuroscience · 2026Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Tissue Fibrosis Decoded via Cellular Senescence: Mechanisms, Treatments, and Emerging Technologies.Aging and disease · 2025Review
- The Quest for Eternal Youth: Hallmarks of Aging and Rejuvenating Therapeutic Strategies.Biomedicines · 2024Review
- Ketogenic diet administration later in life improves memory by modifying the synaptic cortical proteome via the PKA signaling pathway in aging mice.Cell reports. Medicine · 2024Article
- The intersection of sleep and synaptic translation in synaptic plasticity deficits in neurodevelopmental disorders.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2024Review
- Molecular mechanisms of aging and anti-aging strategies.Cell communication and signaling : CCS · 2024Review
- Molecular hallmarks of ageing in amyotrophic lateral sclerosis.Cellular and molecular life sciences : CMLS · 2024Review
- Pharmacological Analysis of GABAInternational journal of molecular sciences · 2023Article
- Proteostasis failure exacerbates neuronal circuit dysfunction and sleep impairments in Alzheimer's disease.Molecular neurodegeneration · 2023Review
- Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection.International journal of molecular sciences · 2023Review
- Early and late chaperone intervention therapy boosts XBP1s and ADAM10, restores proteostasis, and rescues learning in Alzheimer's Disease mice.Aging biology · 2023Article
- Biology of Stress Responses in Aging.Aging biology · 2023Article
- Amide Proton Transfer-Weighted Imaging Detects Hippocampal Proteostasis Disturbance Induced by Sleep Deprivation at 7.0 T MRI.ACS chemical neuroscience · 2022Article
- Unfolded protein response IRE1/XBP1 signaling is required for healthy mammalian brain aging.The EMBO journal · 2022Article
- New Insights into the Molecular Interplay between Human Herpesviruses and Alzheimer's Disease-A Narrative Review.Brain sciences · 2022Review
- Hippocampal Endoplasmic Reticulum Stress Hastens Motor and Cognitive Decline in Adult Male Rats Sustainedly Exposed to High-Sucrose Diet.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
As the aging population grows, the need to understand age-related changes in health is vital. Two prominent behavioral changes that occur with age are disrupted sleep and impaired cognition. Sleep disruptions lead to perturbations in proteostasis and endoplasmic reticulum (ER) stress in mice. Further, consolidated sleep and protein synthesis are necessary for memory formation. With age, the molecular mechanisms that relieve cellular stress and ensure proper protein folding become less efficient. It is unclear if a causal relationship links proteostasis, sleep quality, and cognition in aging. Here, we used a mouse model of aging to determine if supplementing chaperone levels reduces ER stress and improves sleep quality and memory. We administered the chemical chaperone 4-phenyl butyrate (PBA) to aged and young mice, and monitored sleep and cognitive behavior. We found that chaperone treatment consolidates sleep and wake, and improves learning in aged mice. These data correlate with reduced ER stress in the cortex and hippocampus of aged mice. Chaperone treatment increased p-CREB, which is involved in memory formation and synaptic plasticity, in hippocampi of chaperone-treated aged mice. Hippocampal overexpression of the endogenous chaperone, binding immunoglobulin protein (BiP), improved cognition, reduced ER stress, and increased p-CREB in aged mice, suggesting that supplementing BiP levels are sufficient to restore some cognitive function. Together, these results indicate that restoring proteostasis improves sleep and cognition in a wild-type mouse model of aging. The implications of these results could have an impact on the development of therapies to improve health span across the aging population.
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