Role of pyroptosis in the pathogenesis of various neurological diseases.

Pyroptosis, an inflammatory programmed cell death process, has recently garnered significant attention due to its pivotal role in various neurological diseases. This review delves into the intricate molecular signaling pathways governing pyroptosis, encompassing both caspase-1 dependent and caspase-1 independent routes, while emphasizing the critical role played by the inflammasome machinery in initiating cell death. Notably, we explore the Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, the Absent in melanoma 2-like receptor family, and the Pyrin receptor family as essential activators of pyroptosis. Additionally, we comprehensively examine the Gasdermin family, renowned for their role as executioner proteins in pyroptosis. Central to our review is the interplay between pyroptosis and various central nervous system (CNS) cell types, including astrocytes, microglia, neurons, and the blood-brain barrier (BBB). Pyroptosis emerges as a significant factor in the pathophysiology of each cell type, highlighting its far-reaching impact on neurological diseases. This review also thoroughly addresses the involvement of pyroptosis in specific neurological conditions, such as HIV infection, drug abuse-mediated pathologies, Alzheimer's disease, and Parkinson's disease. These discussions illuminate the intricate connections between pyroptosis, chronic inflammation, and cell death in the development of these disorders. We also conducted a comparative analysis, contrasting pyroptosis with other cell death mechanisms, thereby shedding light on their unique aspects. This approach helps clarify the distinct contributions of pyroptosis to neuroinflammatory processes. In conclusion, this review offers a comprehensive exploration of the role of pyroptosis in various neurological diseases, emphasizing its multifaceted molecular mechanisms within various CNS cell types. By elucidating the link between pyroptosis and chronic inflammation in the context of neurodegenerative disorders and infections, it provides valuable insights into potential therapeutic targets for mitigating these conditions.

Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages.

Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus' host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum-two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.