The normal function of prion protein (PrP) is usually disregarded at the expense of the more fascinating role of PrP in transmissible prion diseases. However, the normal PrP may play an important role in cellular function in the central nervous system, since PrP is highly expressed in neurons and motifs in the sequence of PrP are conserved in evolution. The finding that prion null mice do not have a significant overt phenotype suggests that the normal function of PrP is of minor importance. However, the absence of PrP in cells or in vivo contributes to an increased susceptibility to oxidative stress or apoptosis-inducing insults. An alternative explanation is that the PrP normal function is so important that it is redundant. Probing into the characteristics of PrP has revealed a number of features that could mediate important cellular functions. The neuroprotective actions so far identified with PrP are initiated through cell surface signaling, antioxidant activity, or anti-Bax function. Here, we review the characteristics of the PrP and the evidence that PrP protects against neurodegeneration and neuronal cell death.

RNA vaccines have demonstrated efficacy against SARS-CoV-2 in humans and the technology, is being leveraged for rapid emergency response. In this report, we assessed immunogenicity, and, for the first time, toxicity, biodistribution and protective efficacy in preclinical models of a two-dose self-amplifying messenger RNA (SAM) vaccine, encoding a prefusion stabilized Spike antigen of SARS-CoV-2 Wuhan-Hu-1 strain and delivered by lipid nanoparticles (LNP). In mice, one immunization with the SAM vaccine elicited a robust Spike-specific antibody response, which was further boosted by a second immunization, and effectively neutralized the matched SARS-CoV-2 Wuhan strain as well as B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.2 (Delta) variants. High frequencies of Spike-specific germinal center B, Th0/Th1 CD4, and CD8 T cell responses were observed in mice. Local tolerance, potential systemic toxicity, and biodistribution of the vaccine were characterized in rats. In hamsters, the vaccine candidate was well-tolerated, markedly reduced viral load in the upper and lower airways, and protected animals against disease in a dose-dependent manner, with no evidence of disease enhancement following SARS-CoV-2 challenge. Therefore, the SARS-CoV-2 SAM (LNP) vaccine candidate has a favorable safety profile, elicits robust protective immune responses against multiple SARS-CoV-2 variants, and has been advanced to Phase-1 clinical evaluation (NCT04758962).

The combination of radiography, regional ultrasonography, and magnetic resonance imaging enabled lesion structure and cavity content evaluation. However, final diagnosis was confirmed by histologic evaluation. To our knowledge, this is the first veterinary report of the use of magnetic resonance imaging in the characterization and diagnosis of an ABC.

Prion protein inhibits Bax activation and Bax-mediated cell death in primary cultures of human neurons and in MCF-7 cells. To determine whether prion protein can protect against Bax-mediated cell death in vivo, wild-type, null and prion over-expressing mice were subjected to Bax-dependent ethanol induced neuronal apoptotic cell death and the brains were immunostained for active caspase-3 as a downstream marker of Bax activation. Bax activation occurs in all ethanol-injected mice independent of their genotype. A higher level of cell death is present in ethanol-injected null mice than in wild-type and prion over-expressing mice. We conclude that prion protein protects some, but not all neurons, against Bax-mediated cell death in this experimental paradigm.

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In the 1700's a strange new disease affecting sheep was recognized in Europe. The disease later became known as “Scrapie” and was the first of a family of similar diseases affecting a number of species that are now known as the Transmissible Spongiform Encephalopathies (TSEs). The appearance of a new disease in humans linked to the consumption of meat products from infected cattle has stimulated widespread public concern and scientific interest in the prion protein and related diseases. Nearly 300 years after the first report, these diseases still merit the descriptor “strange”. This family of diseases is characterized by a unique profile of histological changes, can be transmitted as inherited or acquired diseases, as well as apparent sporadic spontaneous generation of the disease. These diseases are believed by many, to be caused by a unique protein only infectious agent. The “prion protein” (PrPC), a term first coined by Stanley Prusiner in 1982 is crucial to the development of these diseases, apparently by acting as a substrate for an abnormal disease associated form. However, aside from being critical to the pathogenesis of the disease, the function of PrPC, which is expressed in all mammals, has defied definitive description. Several roles have been proposed on the basis ofin vitrostudies, however, thus far,in vivoconfirmation has not been forthcoming. The biological features of PrPCalso seem to be unusual. Numerous mouse models have been generated in an attempt to understand the pathogenesis of these diseases. This review summarizes the current state of histological features, the etiologic agent, the normal metabolism and the function of the prion protein, as well as the limitations of the mouse models.

BackgroundAge and rate of acoustic stimulation affect peak latencies in brainstem auditory evoked responses (BAER) in humans. Those effects are unknown in foals.Hypothesis/ObjectivesOur goals were to (1) establish reference values for BAER in foals by using 3 different stimulation protocols, (2) evaluate the effects of age and stimulation frequencies on BAER tracing in foals up to 6 months old, and (3) compare the data with BAER obtained from foals with central nervous system (CNS) disorders.AnimalsThirty‐nine neurologically normal foals and 16 foals with neurologic diseases.MethodsProspective observational clinical study. BAER recorded by using 3 protocols of stimulation (11.33 repetitions per second [Hz]/70 decibel normal hearing level [dBNHL]; 11.33 Hz/90 dBNHL; 90 Hz/70 dBNHL).ResultsNo effect of age was observed in normal foals (P > .005). No significant difference was observed for latencies and interpeak latencies (IPL) when comparing foals with neurologic diseases and normal foals (P > .05), but 78.6% of foals with neurologic diseases had an asymmetry in their tracing, reflecting a difference in conduction time between the left and right side of the brainstem. Increasing the stimulation rate did not improve detection of CNS disorders.Conclusions and Clinical ImportanceWe propose BAER reference values for foals up to 6 months of age by using 3 protocols. Most foals with neurologic deficits had abnormal BAER tracing.

The syndrome of AFE was not reproduced in this rabbit model. However, injection of autologous amniotic fluid induced a transient and severe thrombocytopenia. Moreover, TEG analysis indicated that amniotic fluid could initiate the coagulation cascade. Other factors such as the presence of meconium in amniotic fluid may be needed to provoke more severe clinical signs.