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

A family of semifields in characteristic 2

We construct and describe the basic properties of a family of semifields in characteristic $2.$ The construction relies on the properties of projective polynomials over finite fields. We start by associating non-associative products to each such polynomial. The resulting presemifields form the degenerate case of our family. They are isotopic to the Knuth semifields which are quadratic over left and right nucleus. The non-degenerate members of our family display a very different behaviour. Their left and right nucleus agrees with the center, the middle nucleus is quadratic over the center. None of those semifields is isotopic or Knuth equivalent to a commutative semifield. As a by-product we obtain the complete taxonomy of the characteristic $2$ semifields which are quadratic over the middle nucleus, bi-quadratic over the left and right nucleus and not isotopic to twisted fields. This includes {determining} when two such semifields are isotopic and the order of the autotopism group.Comment: 23 page