Nonno, R. | bioRxiv Science

bioRxiv2025

First identification of camel prion disease in Tataouine, Tunisia: an emerging animal prion disease in North Africa

Prion diseases are fatal neurodegenerative disorders affecting humans and animals. Among these, camel prion disease (CPrD) was recently identified in Algeria as a novel disease. In this study, we report six CPrD cases in dromedary camels (Camelus dromedarius) from Tunisia, providing further evidence of its occurrence in North Africa. Affected animals exhibited neurological signs and showed PrPSc accumulation in both brain and lymphoid tissues. Molecular and pathological analyses revealed features consistent with Algerian CPrD cases and distinct from classical scrapie and bovine spongiform encephalopathy. The detection of PrPSc in lymphoid organs, together with the relatively young age of some affected individuals, suggests the possibility of a contagious etiology, including potential vertical or early-life transmission mechanisms, as observed in scrapie and chronic wasting disease affecting small ruminants and cervids, respectively. These findings underscore the need for continued surveillance and further investigation into the epidemiology, transmission mechanisms and potential public health implications of CPrD.

microbiology↗

bioRxiv2023

Cleavage site-directed antibodies reveal the prion protein in humans is shed by ADAM10 at Y226 and associates with misfolded protein deposits in neurodegenerative diseases

Proteolytic cell surface release ( shedding) of the prion protein (PrP), a broadly expressed GPI-anchored glycoprotein, by the metalloprotease ADAM10 impacts on neurodegenerative and other diseases in animal and in vitro models. Recent studies employing the latter also suggest shed PrP (sPrP) to be a ligand in intercellular communication and critically involved in PrP-associated physiological tasks. Although expectedly an evolutionary conserved event, and while soluble forms of PrP are present in human tissues and body fluids, neither proteolytic PrP shedding and its cleavage site nor involvement of ADAM10 or the biological relevance of this process have been demonstrated for the human body thus far. In this study, cleavage site prediction and generation (plus detailed characterization) of sPrP-specific antibodies enabled us to identify PrP cleaved at tyrosin 226 as the physiological and strictly ADAM10-dependent shed form in humans. Using cell lines, neural stem cells and brain organoids, we show that shedding of human PrP can be stimulated by PrP-binding ligands without targeting the protease, which may open novel therapeutic perspectives. Site-specific antibodies directed against human sPrP also detect the shed form in brains of cattle, sheep and deer, hence in all most relevant species naturally affected by fatal and transmissible prion diseases. In human and animal prion diseases, but also in patients with Alzheimers disease, sPrP relocalizes from a physiological diffuse tissue pattern to intimately associate with extracellular aggregates of misfolded proteins characteristic for the respective pathological condition. Findings and research tools presented here will accelerate novel insight into the roles of PrP shedding (as a process) and sPrP (as a released factor) in neurodegeneration and beyond.

neuroscience↗