Protein Acylation Modifications in Sleep Disorders: Mechanisms and Therapeutic Potential

Feb 26, 2026Journal of molecular neuroscience : MN

Protein Acylation Changes in Sleep Disorders: How They Work and Possible Treatments

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Protein acylation may be an important regulatory component in the mechanisms associated with sleep disorders.

Diverse acylation modifications, including acetylation and palmitoylation, could influence various proteins related to the circadian rhythm and neural function.
Most lysine acylation events occur at low levels in normal conditions but may increase at specific sites under pathological states.
These modifications are associated with oxidative stress, neuroinflammation, and disruptions in the circadian cycle based on preclinical evidence.
Robust causal and quantitative evidence linking these acylation events to sleep disorders in humans is currently limited.

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Protein acylation represents a class of metabolism-dependent post-translational modifications that are increasingly recognized as emerging regulatory components implicated in the molecular mechanisms associated with sleep disorders. Accumulating experimental evidence indicates that diverse acylation modifications-including acetylation, lactylation, crotonylation, succinylation, and lipid-type modifications such as palmitoylation and myristoylation-may influence circadian clock proteins, neurotrophic factors, synaptic scaffolding molecules, and mitochondrial energy metabolism. Importantly, most lysine acylation events occur at low global stoichiometry under physiological conditions, whereas pathological metabolic states may induce relative enrichment at specific functional sites rather than widespread high-occupancy modification. These acylation events have been linked to oxidative stress, neuroinflammation, and circadian disruption in preclinical studies, while robust causal and quantitative evidence in humans remains limited. This review synthesizes current mechanistic insights, emphasizes emerging conceptual advances, and outlines key challenges and future directions for translational research in sleep medicine.

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Protein Acylation Modifications in Sleep Disorders: Mechanisms and Therapeutic Potential

Abstract

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