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This report aims to describe the identification of PAstV3 RNA in the central nervous system of weaned pigs with clinical signs of neurological disease associated with polioencephalomyelitis in southeastern Brazil. Three, 20 -35 days-old piglets that died after clinical manifestations of a neurological syndrome were submitted to post-mortem evaluations. Tissue samples were examined by histopathology, bacteriology, and molecular assays (RT-PCR, nested-PCR, RT-qPCR, and Sanger sequencing) to detect the primary infectious disease agents associated with neurological disease in pigs. The principal neuropathological alterations occurred in the grey matter of the spinal cord and brainstem resulting in nonsuppurative poliomyelitis and rhombencephalitis. PAstV3 RNA was detected in the central nervous system samples of all piglets with histopathological evidence of disease and was confirmed by nucleotide sequencing. Nucleic acid from pathogens commonly associated with neurological diseases in pigs, such as porcine teschovirus, porcine sapelovirus, porcine enterovirus G, atypical porcine pestivirus, senecavirus A, and encephalomyocarditis virus was not detected by molecular assays in the three piglets. This is the first report of PAstV3 in piglets with neurological disease and lesions consistent with polioencephalomyelitis in Brazil. This report highlights the importance of monitoring health events that could compromise pig farming productivity and animal welfare.

In the human brain, palmitic acid (16:0; PAM) comprises nearly half of total brain saturates and has been identified as the third most abundant fatty acid overall. Brain PAM supports the structure of membrane phospholipids, provides energy, and regulates protein stability. Sources underlying the origin of brain PAM are both diet and endogenous synthesis via de novo lipogenesis (DNL), primarily from glucose. However, studies investigating the origin of brain PAM are limited to tracer studies utilizing labelled (14C/11C/3H/2H) PAM, and results vary based on the model and tracer used. Nevertheless, there is evidence PAM is synthesized locally in the brain, in addition to obtained directly from the diet. Herein, we provide an overview of brain PAM origin, entry to the brain, metabolic fate, and factors influencing brain PAM kinetics and levels, the latter in the context of age, as well as neurological diseases and psychiatric disorders. Additionally, we briefly summarize the role of PAM in signaling at the level of the brain. We add to the literature a rudimentary summary on brain PAM metabolism.

Transcription factor EB (TFEB) is a basic Helix-Loop-Helix/Leucine Zipper (bHLHZip) class of DNA-binding proteins, which can control the expression of genes included in the autophagy-lysosomal pathway. TFEB regulates the autophagic flux by enhancing lysosome biogenesis, forming autophagosomes, and fusion with lysosomes, thereby facilitating cellular clearance of pathogenic protein structures. Curcumin is a natural polyphenolic molecule with pharmacological properties that make it a potential therapeutic candidate for a wide range of diseases. One of the important curcumin mechanisms of action includes modulation of autophagy through affecting various signaling components such as TFEB. This review discusses in vitro and in vivo evidence on the effects of curcumin on autophagy process via modulating TFEB activity in different disorders.

In recent times, the nasal region has emerged as a distinctive and dynamic environment where a myriad of microbial communities establish residence from infancy, persisting as both commensal and opportunistic pathogens throughout the lifespan. Understanding the coexistence of microorganisms in respiratory mucosal layers, their potential for infections, and the underlying molecular mechanisms shaping these interactions is crucial for developing efficient diagnostic and therapeutic interventions against respiratory and neurodegenerative diseases. Despite significant strides in understanding the olfactory system\'s nexus with nasal microbiota, comprehensive correlations with neurological diseases still need to be discovered. The nasal microbiome, a sentinel in immune defense, orchestrates a delicate equilibrium that, when disrupted, can precipitate severe respiratory infections, including Chronic Rhinosinusitis, Chronic obstructive pulmonary disorder (COPD), and Asthma, and instigate a cascade effect on central nervous system diseases such as Alzheimer\'s disease (AD), Parkinson\'s disease (PD), and Multiple sclerosis (MS). This review aims to redress this imbalance by meticulously exploring the anatomical and microbiological nuances of the nasal mucosal surface in health and disease. By delineating the molecular intricacies of these interactions, this review unravels the molecular mechanisms that govern the intricate nexus between nasal microbiota dysbiosis, olfactory dysfunction, and the progression of respiratory and neurological diseases.

Neurological and neuromuscular diseases resulting from familial, sporadic, or de novo mutations have devasting personal, familial, and societal impacts. As the initial product of DNA transcription, RNA transcripts and their associated ribonucleoprotein complexes provide attractive targets for modulation by increasing wild-type or blocking mutant allele expression, thus relieving downstream pathological consequences. Therefore, it is unsurprising that many existing and under-development therapeutics have focused on targeting disease-associated RNA transcripts as a frontline drug strategy for these genetic disorders. This review focuses on the current range of RNA targeting modalities using examples of both dominant and recessive neurological and neuromuscular diseases.

The epigenome is a complex framework through which gene expression is precisely and flexibly modulated to incorporate heritable memory and responses to environmental stimuli. It governs diverse cellular processes, including cell fate, disease, and aging. The need to understand this system and precisely control gene expression outputs for therapeutic purposes has precipitated the development of a diverse set of epigenetic editing tools. Here, we review the existing toolbox for targeted epigenetic editing, technical considerations of the current technologies, and opportunities for future development. We describe applications of therapeutic epigenetic editing and their potential for treating disease, with a discussion of ongoing delivery challenges that impede certain clinical interventions, particularly in the brain. With simultaneous advancements in available engineering tools and appropriate delivery technologies, we predict that epigenetic editing will increasingly cement itself as a powerful approach for safely treating a wide range of disorders in all tissues of the body.

The most prevalent rare genetic disease affecting young individuals is spinal muscular atrophy (SMA), which is caused by a loss-of-function mutation in the telomeric gene survival motor neuron (SMN) 1. The high heterogeneity of the SMA pathophysiology is determined by the number of copies of SMN2, a separate centromeric gene that can transcribe for the same protein, although it is expressed at a slower rate. SMA affects motor neurons. However, a variety of different tissues and organs may also be affected depending on the severity of the condition. Novel pharmacological treatments, such as Spinraza, Onasemnogene abeparvovec-xioi, and Evrysdi, are considered to be disease modifiers because their use can change the phenotypes of the patients. Since oxidative stress has been reported in SMA-affected cells, we studied the impact of antioxidant therapy on neural stem cells (NSCs) that have the potential to differentiate into motor neurons. Antioxidants can act through various pathways; for example, some of them exert their function through nuclear factor (erythroid-derived 2)-like 2 (NRF2). We found that curcumin is able to induce positive effects in healthy and SMA-affected NSCs by activating the nuclear translocation of NRF2, which may use a different mechanism than canonical redox regulation through the antioxidant-response elements and the production of antioxidant molecules.

Cell death is one of the most important mechanisms of maintaining homeostasis in our body. Ferroptosis and pyroptosis are forms of necrosis-like cell death. These cell death modalities play key roles in the pathophysiology of cancer, cardiovascular, neurological diseases, and other pathologies. Transition metals are abundant group of elements in all living organisms. This paper presents a summary of ferroptosis and pyroptosis pathways and their connection to significant transition metals, namely zinc (Zn), copper (Cu), molybdenum (Mo), lead (Pb), cobalt (Co), iron (Fe), cadmium (Cd), nickel (Ni), mercury (Hg), uranium (U), platinum (Pt), and one crucial element, selenium (Se). Authors aim to summarize the up-to-date knowledge of this topic.In this review, there are categorized and highlighted the most common patterns in the alterations of ferroptosis and pyroptosis by transition metals. Special attention is given to zinc since collected data support its dual nature of action in both ferroptosis and pyroptosis. All findings are presented together with a brief description of major biochemical pathways involving mentioned metals and are visualized in attached comprehensive figures.This work concludes that the majority of disruptions in the studied metals\' homeostasis impacts cell fate, influencing both death and survival of cells in the complex system of altered pathways. Therefore, this summary opens up the space for further research.

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