Search

Abstract β‐secretase (BACE1) is instrumental in amyloid‐β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology. The research reveals that the anticancer agent 6‐thioguanosine (6‐TG) markedly diminishes BACE1 expression without eliciting cytotoxicity while enhancing microglial phagocytic activity, and ameliorate cognitive impairments with reducing Aβ accumulation in AD mice. Leveraging advanced deep learning‐based tool for target identification, and corroborating with surface plasmon resonance assays, it is elucidated that 6‐TG directly interacts with RAGE, modulating BACE1 expression through the JAK2‐STAT1 pathway and elevating soluble RAGE (sRAGE) levels in the brain. The findings illuminate the therapeutic potential of 6‐TG in ameliorating AD manifestations and advocate for small molecule strategies to increase brain sRAGE levels, offering a strategic alternative to the challenges posed by the complexity of AD.

The detailed investigation done on the relationship between the electrocatalytic performance of PtRu catalysts and the characteristics of the carbon supports is presented. Catalysts supported on carbon materials with specific characteristics such as a highly graphitic structure showed improved catalytic activities as a result of a preferred crystallographic orientation by interactions with the highly ordered substrate.