Background: Moderate physical exercise is conducive to the brains of healthy humans and AD patients. Previous reports have suggested that treadmill exercise plays an anti-AD role and improves cognitive ability by promoting amyloid clearance, inhibiting neuronal apoptosis, reducing oxidative stress level, alleviating brain inflammation, and promoting autophagy–lysosome pathway in AD mice. However, few studies have explored the relationships between the ubiquitin–proteasome system and proper exercise in AD. The current study was intended to investigate the mechanism by which the exercise-regulated E3 ubiquitin ligase improves AD.Methods: Both wild type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 12 for each group). WTE and ADE mice were subjected to treadmill exercise of 12 weeks in order to assess the effect of treadmill running on learning and memory ability, Aβ plaque burden, hyperphosphorylated Tau protein and E3 ubiquitin ligase.Results: The results indicated that exercise restored learning and memory ability, reduced Aβ plaque areas, inhibited the hyperphosphorylation of Tau protein activated PI3K/Akt/Hsp70 signaling pathway, and improved the function of the ubiquitin–proteasome system (increased UCHL-1 and CHIP levels, decreased BACE1 levels) in APP/PS1 transgenic mice.Conclusions: These findings suggest that exercise may promote the E3 ubiquitin ligase to clear β-amyloid and hyperphosphorylated Tau by activating the PI3K/Akt signaling pathway in the hippocampus of AD mice, which is efficient in ameliorating pathological phenotypes and improving learning and memory ability.

Despite being one of the greatest global challenges for health and social care in the 21st century, Alzheimer’s disease (AD) lacks specific medicine. Irisin, an exercise-generated muscle factor, emerges as a potential hormone for AD prevention and treatment because of its role in promoting the browning of white adipose tissue, accelerating energy expenditure, regulating energy metabolism, and improving insulin resistance. The study reviews classic hallmarks of AD and irisin’s physiology before discussing the possible mechanism by which irisin protects against AD in terms of its effects related to molecular biology and cellular biology. Results reveal that irisin sharpens learning memory by inducing the production of brain-derived neurotrophic factor (BDNF), lowers the production of inflammatory factors, protects neurology through astrocytes, and ameliorates AD symptoms by improving insulin resistance. The review aims to facilitate future experimental studies and clinical applications of irisin in preventing and treating AD.

Introduction: Lactate is a key biomarker for clinical diagnostics and athletic performance monitoring. Conventional blood-based assays are invasive and not ideal for real-time applications. Sweat, as a non-invasive alternative, offers significant advantages for dynamic lactate tracking.Methods: We developed a highly sensitive fluorescence resonance energy transfer (FRET)-based aptasensor for lactate detection in sweat. The sensing platform utilizes aptamer-functionalized core–shell upconversion nanoparticles (APT-CS-UCNPs) as energy donors and Fe₃O₄-decorated molybdenum disulfide (MoS₂) nanosheets as quenchers. In the absence of lactate, efficient FRET occurs due to the close proximity (<10 nm) between the donor and acceptor, quenching fluorescence at 545 nm. Lactate binding induces conformational changes in the aptamer, increasing donor–acceptor distance and restoring fluorescence intensity.Results: The aptasensor exhibited a broad linear detection range (0–30 mM, R² = 0.9981) and an ultralow detection limit (0.07785 mM), outperforming most reported electrochemical sensors. In spiked sweat samples, recovery rates ranged from 98.45% to 104.28%, with negligible cross-reactivity to common interferents. Comparative analysis with commercial kits and previously published methods confirmed superior sensitivity and ease of operation.Discussion: This FRET-based aptasensor enables accurate, rapid, and non-invasive lactate quantification using standard laboratory instrumentation. Its successful application in real human sweat samples highlights strong potential for both clinical diagnostics and athletic performance monitoring.