Disintegration of Cav-1/ß-catenin complex attenuates neuronal death after ischemia-reperfusion injury by promoting ß-catenin nuclear translocation.

BACKGROUND: The roles of Caveolin-1 (Cav-1) and the Wnt/ß-catenin signaling pathways in cerebral ischemia-reperfusion (I/R) injury are well established. The translocation of ß-catenin into the nucleus is critical for regulating neuronal apoptosis, repair, and neurogenesis within the ischemic brain. It has been reported that the scaffold domain of Caveolin-1 (Cav-1) (residues 95-98) interacts with ß-catenin (residues 330-337). However, the specific contribution of the Cav-1/ß-catenin complex to I/R injury remains unknown. METHODS AND RESULTS: To investigate the mechanism underlying the involvement of the Cav-1/ß-catenin complex in the subcellular translocation of ß-catenin and its subsequent effects on cerebral I/R injury, we treated ischemic brains with ASON (Cav-1 antisense oligodeoxynucleotides) or FTVT (a competitive peptide antagonist of the Cav-1 and ß-catenin interaction). Our study demonstrated that the binding of Cav-1 to ß-catenin following I/R injury prevented the nuclear accumulation of ß-catenin. Treatment with ASON or FTVT after I/R injury significantly increased the levels of nuclear ß-catenin. Furthermore, ASON reduced the phosphorylation of ß-catenin at Ser33, Ser37, and Thr41, which contributes to its proteasomal degradation, while FTVT increased phosphorylation at Tyr333, which is associated with its nuclear translocation. CONCLUSIONS: The above results indicate that the formation of the Cav-1/ß-catenin complex anchors ß-catenin in the cytoplasm following I/R injury. Additionally, both ASON and FTVT treatments attenuated neuronal death in ischemic brains. Our study suggests that targeting the interaction between Cav-1 and ß-catenin serve as a novel therapeutic strategy to protect against neuronal damage during cerebral injury.

Aerobic exercise suppresses cognitive injury in patients with Alzheimer's disease by regulating long non-coding RNA TUG1.

BACKGROUND: Alzheimer's disease (AD) is the primary reason for disability of the elderly. This article studied the diagnostic possibility of TUG1 and its potential mechanism in the regulation of aerobic exercise (AE) on AD. METHODS: 77 AD patients undertook a three-month-long cycling exercise, and 77 healthy controls were recruited. Polymerase Chain Reaction amplification was applied to assess the expression of TUG1 and miR-129-5p. The diagnostic possibility was manifested by the receiver operating characteristic (ROC) curve. Spearman correlation analyzed the interrelationships between TUG1 and AD. In vivo, the APP/PS1 double transgenic mouse models of AD were included for rescue experiments. Morris water maze (MWM) was performed to assess cognitive function of AD mice. RESULTS: The content of TUG1 was ascended in AD patients and was diminished after AE. The increase of TUG1 indicated the high risk of the occurrence of AD. TUG1 was closely connected to the cognitive assessment tools of AD patients. The TUG1/ miR-129-5p axis was the regulator of the regulation of AE in AD mice. CONCLUSION: TUG1 was involved in AD development and targeted miR-129-5p to participate in the regulation of AE.