Extracellular Matrix Remodeling Alleviates Memory Deficits in Alzheimer's Disease by Enhancing the Astrocytic Autophagy-Lysosome Pathway.

Extracellular matrix (ECM) remodeling is strongly linked to Alzheimer's disease (AD) risk; however, the underlying mechanisms are not fully understood. Here, it is found that the injection of chondroitinase ABC (ChABC), mimicking ECM remodeling, into the medial prefrontal cortex (mPFC) reversed short-term memory loss and reduced amyloid-beta (Aß) deposition in 5xFAD mice. ECM remodeling also reactivated astrocytes, reduced the levels of aggrecan in Aß plaques, and enhanced astrocyte recruitment to surrounding plaques. Importantly, ECM remodeling enhanced the autophagy-lysosome pathway in astrocytes, thereby mediating Aß clearance and alleviating AD pathology. ECM remodeling also promoted Aß plaque phagocytosis by astrocytes by activating the astrocytic phagocytosis receptor MERTK and promoting astrocytic vesicle circulation. The study identified a cellular mechanism in which ECM remodeling activates the astrocytic autophagy-lysosomal pathway and alleviates AD pathology. Targeting ECM remodeling may represent a potential therapeutic strategy for AD and serve as a reference for the treatment of this disease.

Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways.

Cathepsin B (CatB), a cysteine protease, is primarily localized within subcellular endosomal and lysosomal compartments. It is involved in the turnover of intracellular and extracellular proteins. Interest is growing in CatB due to its diverse roles in physiological and pathological processes. In functional defective tissues, programmed cell death (PCD) is one of the regulable fundamental mechanisms mediated by CatB, including apoptosis, pyroptosis, ferroptosis, necroptosis, and autophagic cell death. However, CatB-mediated PCD is responsible for disease progression under pathological conditions. In this review, we provide an overview of the critical roles and regulatory pathways of CatB in different types of PCD, and discuss the possibility of CatB as an attractive target in multiple diseases. We also summarize current gaps in the understanding of the involvement of CatB in PCD to highlight future avenues for research.

Grapevine bZIP transcription factor bZIP45 regulates VvANN1 and confers drought tolerance in Arabidopsis.

Drought is a severe environmental condition that restricts the vegetative growth and reduces the yield of grapevine (Vitis vinifera L.). However, the mechanisms underlying grapevine response and adaptation to drought stress remain unclear. In the present study, we characterized an ANNEXIN gene, VvANN1, which plays a positive role in the drought stress response. The results indicated that VvANN1 was significantly induced by osmotic stress. Expression of VvANN1 in Arabidopsis thaliana enhanced osmotic and drought tolerance through modulating the level of MDA, H2O2, and O2 ·- at the seedling stage, implying that VvANN1 might be involved in the process of ROS homeostasis under drought or osmotic stress conditions. Moreover, we used yeast one-hybridization and chromatin immunoprecipitation assays to show that VvbZIP45 could regulate VvANN1 expression by directly binding to the promoter region of VvANN1 in response to drought stress. We also generated transgenic Arabidopsis that constitutively expressed the VvbZIP45 gene (35S::VvbZIP45) and further produced VvANN1Pro::GUS/35S::VvbZIP45 Arabidopsis plants via crossing. The genetic analysis results subsequently indicated that VvbZIP45 could enhance GUS expression in vivo under drought stress. Our findings suggest that VvbZIP45 may modulate VvANN1 expression in response to drought stress and reduce the impact of drought on fruit quality and yield.

Mirror image pain mediated by D2 receptor regulation of astrocytic Cx43 phosphorylation and channel opening.

Mirror image pain (MIP), a clinical syndrome of contralateral pain hypersensitivity caused by unilateral injury, has been identified in various neuropathological conditions. Gap junctional protein Connexin 43 (Cx43), its phosphorylation levels and dopamine D2 receptor (DRD2) play key integrating roles in pain processing. We presume D2DR activity may affect Cx43 hemichannel opening via Cx43 phosphorylation levels to regulate MIP. This study shows that spinal astrocytic Cx43 directly interacts with DRD2 to mediate MIP. DRD2 and Cx43 expression levels were asymmetrically elevated in bilateral spinal during MIP, and DRD2 modulated the opening of primary astrocytic Cx43 hemichannels. Furthermore, Cx43 phosphorylation at Ser373 was increased during MIP, but decreased in DRD2 knockout (KO) mice. Finally, activation of spinal protein kinase A (PKA) altered the expression of Cx43 and its phosphorylation bilaterally, thus reversing the analgesic effect in DRD2 KO mice. Together, these data reveal that spinal Cx43 phosphorylation and channel opening are regulated by DRD2 via PKA activation, and that spinal Cx43 and DRD2 are key molecular sensors mediating mirror image pain.

Spectroscopic investigation of the interaction between copper (II) 2-oxo-propionic acid salicyloyl hydrazone complex and bovine serum albumin.

The interaction between copper (II) 2-oxo-propionic acid salicyloyl hydrazone (Cu(II)L) and bovine serum albumin (BSA) under physiological conditions was investigated by the methods of fluorescence spectroscopy, UV-Vis absorption, and circular dichroism spectroscopy. Fluorescence data showed that the fluorescence quenching of BSA by Cu(II)L was the result of the formation of the BSA-Cu(II)L complex. The apparent binding constants (K (a)) between Cu(II)L and BSA at four different temperatures were obtained according to the modified Stern-Volmer equation. The thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS), for the reaction were calculated to be -80.79 kJ mol(-1) and -175.48 J mol(-1) K(-1) according to van't Hoff equation. The results indicated that van der Waals force and hydrogen bonds were the dominant intermolecular force in stabilizing the complex. The binding distance (r) between Cu(II)L and the tryptophan residue of BSA was obtained to be 4.1 nm according to Förster's nonradioactive energy transfer theory. The conformational investigation showed that the application of Cu(II)L increased the hydrophobicity of amino acid residues and decreased the alpha-helical content of BSA (from 62.71% to 37.31%), which confirmed some microenvironmental and conformational changes of BSA molecules.