The Endoplasmic Reticulum Stress Response in Neuroprogressive Diseases: Emerging Pathophysiological Role and Translational Implications

The endoplasmic reticulum (ER) is the main cellular organelle involved in protein synthesis, assembly and secretion. Accumulating evidence shows that across several neurodegenerative and neuroprogressive diseases, ER stress ensues, which is accompanied by over-activation of the unfolded protein response (UPR). Although the UPR could initially serve adaptive purposes in conditions associated with higher cellular demands and after exposure to a range of pathophysiological insults, over time the UPR may become detrimental, thus contributing to neuroprogression. Herein, we propose that immune-inflammatory, neuro-oxidative, neuro-nitrosative, as well as mitochondrial pathways may reciprocally interact with aberrations in UPR pathways. Furthermore, ER stress may contribute to a deregulation in calcium homoeostasis. The common denominator of these pathways is a decrease in neuronal resilience, synaptic dysfunction and even cell death. This review also discusses how mechanisms related to ER stress could be explored as a source for novel therapeutic targets for neurodegenerative and neuroprogressive diseases. The design of randomised controlled trials testing compounds that target aberrant UPR-related pathways within the emerging framework of precision psychiatry is warranted

The symbolic meaning of cattle and sheep/goat in the Bronze Age: Faunal inclusions in funerary contexts of South-Western Iberia

The inclusion of faunal remains in funerary practices is widely documented in Iberian prehistory. For the late prehistory (Neolithic to Bronze Age), there is relatively more data than in earlier periods, with limb segments being very common, and complete animals are rarer. In Bronze Age contexts from South-Western Iberia, a high percentage of human burials in subterranean chambers (hypogea) are associated with limb bones of cattle (Bos taurus) and sheep/goats (Ovis/Capra), along with other grave goods. Traditionally, this practice is interpreted as the result of rituals of commensality. In this paper, we present a different perspective. Besides commensality, we show that the inclusion of the same species and the same anatomical parts is a highly standardised behaviour. Beyond the tight connection between humans and animals, this pattern also points to a strong symbolism of these domestic species and to symbolic meaning of the anatomical parts themselves.info:eu-repo/semantics/publishedVersio