The widespread increase in multiple severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants is causing a significant health concern in the United States and worldwide. These variants exhibit increased transmissibility, cause more severe disease, exhibit evasive immune properties, impair neutralization by antibodies from vaccinated individuals or convalescence sera, and reinfection. The Centers for Disease Control and Prevention (CDC) has classified SARS-CoV-2 variants into variants of interest, variants of concern, and variants of high consequence. Currently, four variants of concern (B.1.1.7, B.1.351, P.1, and B.1.617.2) and several variants of interests (B.1.526, B.1.525, and P.2) are characterized and are essential for close monitoring. In this review, we discuss the different SARS-CoV-2 variants, emphasizing variants of concern circulating the world and highlight the various mutations and how these mutations affect the characteristics of the virus. In addition, we discuss the most common vaccines and the various studies concerning the efficacy of these vaccines against different variants of concern.

As the kynurenine pathway’s links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson’s, Alzheimer’s, Huntington’s Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.

There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS–STING signaling pathway and the mechanisms underlying the association between cGAS–STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS–STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS–STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs

The brain contains various forms of lipids that are important for maintaining its structural integrity and regulating various signaling cascades. Autotaxin (ATX) is an ecto-nucleotide pyrophosphatase/phosphodiesterase-2 enzyme that hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid (LPA). LPA is a major bioactive lipid which acts through G protein-coupled receptors (GPCRs) and plays an important role in mediating cellular signaling processes. The majority of synthesized LPA is derived from membrane phospholipids through the action of the secreted enzyme ATX. Both ATX and LPA are highly expressed in the central nervous system. Dysfunctional expression and activity of ATX with associated changes in LPA signaling have recently been implicated in the pathogenesis of Alzheimer’s disease (AD). This review focuses on the current understanding of LPA signaling, with emphasis on the importance of the autotaxin–lysophosphatidic acid (ATX–LPA) pathway and its alterations in AD and a brief note on future therapeutic applications based on ATX–LPA signaling.

Neurodegenerative diseases are characterized by progressive loss of neurons in specific regions of the brain. Neuronal death is often associated with the accumulation of misfolded proteins due to genetic mutations or abnormal protein homeostasis. An essential mechanism for regulating the clearance of misfolded proteins is neddylation, a post-translational modification closely related to ubiquitination. Neddylation is brought about by conjugating neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to target substrates through a cascade of cellular events. Neddylation is crucial for many biological processes, and dysfunctional neddylation is implicated in several neurodegenerative diseases. This review discusses the current understanding of the role of neddylation pathways in neurodegenerative disorders and the emergence of neddylation signaling as a potential target for drug discovery and development in neurodegenerative diseases.