The Collagen Chaperone HSP47 Is a New Interactor of APP that Affects the Levels of Extracellular Beta-Amyloid Peptides

Alzheimer disease (AD) is a neurodegenerative disorder characterized by progressive decline of cognitive function that represents one of the most dramatic medical challenges for the aging population. Aβ peptides, generated by processing of the Amyloid Precursor Protein (APP), are thought to play a central role in the pathogenesis of AD. However, the network of physical and functional interactions that may affect their production and deposition is still poorly understood. The use of a bioinformatic approach based on human/mouse conserved coexpression allowed us to identify a group of genes that display an expression profile strongly correlated with APP. Among the most prominent candidates, we investigated whether the collagen chaperone HSP47 could be functionally correlated with APP. We found that HSP47 accumulates in amyloid deposits of two different mouse models and of some AD patients, is capable to physically interact with APP and can be relocalized by APP overexpression. Notably, we found that it is possible to reduce the levels of secreted Aβ peptides by reducing the expression of HSP47 or by interfering with its activity via chemical inhibitors. Our data unveil HSP47 as a new functional interactor of APP and imply it as a potential target for preventing the formation and/or growth amyloid plaques

Intended and Unintended Consequences of Forced Migrations: A Neglected Aspect of East Europe's 20th Century History

The article examines the consequences, thus far under-investigated in transnational migration studies, of forced population movements for the societies and cultures of the sending/expelling countries. The cases considered are immense forced migrations, involving over 80 million people, across and outside Eastern Europe during the twentieth century. The discussion focuses on the consequences of these involuntary movements in the public sphere, including effects on the collective (group) self-perceptions and representations of others (non-group) and inter- and intra-group relations; on national/ethnic culture (collective memory, customs, value orientations); on domestic and international relations; and on human resources (skills, abilities) and economic growth. </jats:p