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Claudin‐10b is an important component of the tight junction in the thick ascending limb (TAL) of Henle's loop and allows paracellular sodium transport. In immunofluorescence stainings, claudin‐10b–positive cells exhibited extensive extra staining of basolateral, column‐like structures. The precise localization and function have so far remained elusive. In isolated cortical TAL segments from C57BL/6J mice, kidney‐specific claudin‐10 knockout mice (cKO), and respective litter mates (WT), we investigated the localization and protein expression and function by fluorescence microscopy and electrophysiological measurements. Ultrastructural analysis of TAL in kidney sections was performed by electron microscopy. Claudin‐10b colocalized with the basolateral Na+‐K+ ATPase and the Cl– channel subunit barttin, but the lack of claudin‐10b did not influence the localization or abundance of these proteins. However, the accessibility of the basolateral infolded extracellular space to ouabain or fluorescein was increased by basolateral Ca2+ removal and in the absence of claudin‐10b. Ultrastructural analysis by electron microscopy revealed a widening of basolateral membrane infoldings in cKO in comparison to WT. We hypothesize that claudin‐10b shapes neighboring membrane invaginations by trans interaction to stabilize and facilitate high‐flux salt transport in a water‐tight epithelium. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a devastating age-dependent neurodegenerative disorder. The main hallmarks are impairment of cholinergic system and accumulation in brain of beta-amyloid (Aβ) aggregates, which have been associated with oxidative damage and dyshomeostasis of redox-active biometals. The absence of an efficient treatment that could delay or cure AD has been attributed to the complexity and multifactorial nature of this disease. With this in mind and the recent interest on natural-based drugs, we have explored a set of natural-based hybrid compounds by conjugation of a tacrine moiety with an Sallylcysteine (garlic constituent) or S-propargylcysteine moiety aimed at improving the cholinergic system and neuroprotective capacity. The docking modeling studies allowed the selection of linkers to optimize the bimodal drug interaction with acetylcholinesterase enzyme (AChE) active site. The compounds were evaluated for some representative biological properties, including AChE activity and Aβ aggregation inhibition, as well as for their neuroprotective activity to Aβ- and ROS-induced cellular toxicity. The most promising results were achieved by compounds 9d for the AChE inhibition and 9l for the remarkable prevention of superoxide production and Aβ-induced cellular toxicity. [ABSTRACT FROM AUTHOR]