Correction: Jain et al. Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages. Proteomes 2022, 10, 34.

In the publication [...].

Network pharmacology-based approach to elucidate the pharmacologic mechanisms of natural compounds from Dictyostelium discoideum for Alzheimer's disease treatment.

Alzheimer's disease (AD) is increasingly becoming a major public health concern in our society. While many studies have explored the use of natural polyketides, alkaloids, and other chemical components in AD treatment, there is an urgent need to clarify the concept of multi-target treatment for AD. This study focuses on using network pharmacology approach to elucidate how secondary metabolites from Dictyostelium discoideum affect AD through multi-target or indirect mechanisms. The secondary metabolites produced by D. discoideum during their development were obtained from literature sources and PubChem. Disease targets were selected using GeneCards, DisGeNET, and CTD databases, while compound-based targets were identified through Swiss target prediction and Venn diagrams were used to find intersections between these targets. A network depicting the interplay among disease, drugs, active ingredients, and key target proteins (PPI network) was formed utilizing the STRING (Protein-Protein Interaction Networks Functional Enrichment Analysis) database. To anticipate the function and mechanism of the screened compounds, GO and KEGG enrichment analyses were conducted and visually presented using graphs and bubble charts. After the screening phase, the top interacting targets in the PPI network and the compound with the most active target were chosen for subsequent molecular docking and molecular dynamic simulation studies. This study identified nearly 50 potential targeting genes for each of the screened compounds and revealed multiple signaling pathways. Among these pathways, the inflammatory pathway stood out. COX-2, a receptor associated with neuroinflammation, showed differential expression in various stages of AD, particularly in pyramidal neurons during the early stages of the disease. This increase in COX-2 expression is likely induce by higher levels of IL-1, which is associated with neuritic plaques and microglial cells in AD. Molecular docking investigations demonstrated a strong binding interaction between the terpene compound PQA-11 and the neuroinflammatory receptor COX2, with a substantial binding affinity of -8.4 kcal/mol. Subsequently, a thorough analysis of the docked complex (COX2-PQA11) through Molecular Dynamics Simulation showed lower RMSD, minimal RMSF fluctuations, and a reduced total energy of -291.35 kJ/mol compared to the standard drug. These findings suggest that the therapeutic effect of PQA-11 operates through the inflammatory pathway, laying the groundwork for further in-depth research into the role of secondary metabolites in AD treatment.

14-3-3 proteins-a moonlight protein complex with therapeutic potential in neurological disorder: in-depth review with Alzheimer's disease.

Alzheimer's disease (AD) affects millions of people worldwide and is a gradually worsening neurodegenerative condition. The accumulation of abnormal proteins, such as tau and beta-amyloid, in the brain is a hallmark of AD pathology. 14-3-3 proteins have been implicated in AD pathology in several ways. One proposed mechanism is that 14-3-3 proteins interact with tau protein and modulate its phosphorylation, aggregation, and toxicity. Tau is a protein associated with microtubules, playing a role in maintaining the structural integrity of neuronal cytoskeleton. However, in the context of Alzheimer's disease (AD), an abnormal increase in its phosphorylation occurs. This leads to the aggregation of tau into neurofibrillary tangles, which is a distinctive feature of this condition. Studies have shown that 14-3-3 proteins can bind to phosphorylated tau and regulate its function and stability. In addition, 14-3-3 proteins have been shown to interact with beta-amyloid (Aß), the primary component of amyloid plaques in AD. 14-3-3 proteins can regulate the clearance of Aß through the lysosomal degradation pathway by interacting with the lysosomal membrane protein LAMP2A. Dysfunction of lysosomal degradation pathway is thought to contribute to the accumulation of Aß in the brain and the progression of AD. Furthermore, 14-3-3 proteins have been found to be downregulated in the brains of AD patients, suggesting that their dysregulation may contribute to AD pathology. For example, decreased levels of 14-3-3 proteins in cerebrospinal fluid have been suggested as a biomarker for AD. Overall, these findings suggest that 14-3-3 proteins may play an important role in AD pathology and may represent a potential therapeutic target for the disease. However, further research is needed to fully understand the mechanisms underlying the involvement of 14-3-3 proteins in AD and to explore their potential as a therapeutic target.

Unveiling the Molecular Footprint: Proteome-Based Biomarkers for Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Early and accurate diagnosis of AD is crucial for implementing timely interventions and developing effective therapeutic strategies. Proteome-based biomarkers have emerged as promising tools for AD diagnosis and prognosis due to their ability to reflect disease-specific molecular alterations. There is of great significance for biomarkers in AD diagnosis and management. It emphasizes the limitations of existing diagnostic approaches and the need for reliable and accessible biomarkers. Proteomics, a field that comprehensively analyzes the entire protein complement of cells, tissues, or bio fluids, is presented as a powerful tool for identifying AD biomarkers. There is a diverse range of proteomic approaches employed in AD research, including mass spectrometry, two-dimensional gel electrophoresis, and protein microarrays. The challenges associated with identifying reliable biomarkers, such as sample heterogeneity and the dynamic nature of the disease. There are well-known proteins implicated in AD pathogenesis, such as amyloid-beta peptides, tau protein, Apo lipoprotein E, and clusterin, as well as inflammatory markers and complement proteins. Validation and clinical utility of proteome-based biomarkers are addressing the challenges involved in validation studies and the diagnostic accuracy of these biomarkers. There is great potential in monitoring disease progression and response to treatment, thereby aiding in personalized medicine approaches for AD patients. There is a great role for bioinformatics and data analysis in proteomics for AD biomarker research and the importance of data preprocessing, statistical analysis, pathway analysis, and integration of multi-omics data for a comprehensive understanding of AD pathophysiology. In conclusion, proteome-based biomarkers hold great promise in the field of AD research. They provide valuable insights into disease mechanisms, aid in early diagnosis, and facilitate personalized treatment strategies. However, further research and validation studies are necessary to harness the full potential of proteome-based biomarkers in clinical practice.

miRNA as an Ultimate and Emerging Diagnostic Approach for the Detection of Alzheimer's Disease.

Alzheimer's disease is a prevalent neurodegenerative disorder primarily affecting elderly individuals, characterized by cognitive decline and dysfunction in the nervous system. The disease is hallmarked by the presence of neurofibrillary tangles and amyloid-ß plaques. Approximately 10.7% of the global population aged 65 and above suffer from Alzheimer's disease, and this number is projected to rise significantly in the foreseeable future. By the year 2050, the worldwide prevalence is estimated to reach 139 million cases, compared to the current 55 million cases. The identification of reliable biomarkers that can facilitate the diagnosis and prognosis of Alzheimer's disease is crucial. MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules that play a significant role in mRNA regulation and protein level maintenance through mRNA degradation. Over the past decade, researchers have primarily focused on elucidating the functions and expression patterns of miRNAs in various diseases, including Alzheimer's disease, to uncover their potential as diagnostic biomarkers. This review emphasizes the potential of miRNAs as diagnostic biomarkers for Alzheimer's disease and explores their roles and therapeutic possibilities. MiRNAs possess several features that make them ideal biomarkers, including their ability to be easily detected in body fluids. Moreover, the extraction process is minimally invasive, as miRNAs can be readily extracted. Advances in technology have facilitated the integration of miRNAs into micro-assays, enhancing the reliability and utility of miRNAs as diagnostic biomarkers for Alzheimer's disease.

Probiotics for Neurodegenerative Diseases: A Systemic Review.

Neurodegenerative disorders (ND) are a group of conditions that affect the neurons in the brain and spinal cord, leading to their degeneration and eventually causing the loss of function in the affected areas. These disorders can be caused by a range of factors, including genetics, environmental factors, and lifestyle choices. Major pathological signs of these diseases are protein misfolding, proteosomal dysfunction, aggregation, inadequate degradation, oxidative stress, free radical formation, mitochondrial dysfunctions, impaired bioenergetics, DNA damage, fragmentation of Golgi apparatus neurons, disruption of axonal transport, dysfunction of neurotrophins (NTFs), neuroinflammatory or neuroimmune processes, and neurohumoral symptoms. According to recent studies, defects or imbalances in gut microbiota can directly lead to neurological disorders through the gut-brain axis. Probiotics in ND are recommended to prevent cognitive dysfunction, which is a major symptom of these diseases. Many in vivo and clinical trials have revealed that probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, and Lactobacillus casei, etc.) are effective candidates against the progression of ND. It has been proven that the inflammatory process and oxidative stress can be modulated by modifying the gut microbiota with the help of probiotics. As a result, this study provides an overview of the available data, bacterial variety, gut-brain axis defects, and probiotics' mode of action in averting ND. A literature search on particular sites, including PubMed, Nature, and Springer Link, has identified articles that might be pertinent to this subject. The search contains the following few groups of terms: (1) Neurodegenerative disorders and Probiotics OR (2) Probiotics and Neurodegenerative disorders. The outcomes of this study aid in elucidating the relationship between the effects of probiotics on different neurodegenerative disorders. This systematic review will assist in discovering new treatments in the future, as probiotics are generally safe and cause mild side effects in some cases in the human body.

Investigation of Cannabis sativa Phytochemicals as Anti-Alzheimer's Agents: An In Silico Study.

Cannabis sativa is a medicinal plant that has been known for years and is used as an Ayurvedic medicine. This plant has great potential in treating various types of brain diseases. Phytochemicals present in this plant act as antioxidants by maintaining synaptic plasticity and preventing neuronal loss. Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are both beneficial in treating Alzheimer's disease by increasing the solubility of Aß42 amyloid and Tau aggregation. Apart from these therapeutic effects, there are certain unknown functions of these phytochemicals in Alzheimer's disease that we want to elucidate through this study. In this research, our approach is to analyze the effect of phytochemicals in Cannabis sativa on multiple culprit enzymes in Alzheimer's disease, such as AChE (Acetylcholinesterase), BChE (Butyrylcholinesterase), γ-secretase, and BACE-1. In this study, the compounds were selected by Lipinski's rule, ADMET, and ProTox based on toxicity. Molecular docking between the selected compounds (THCV, Cannabinol C2, and Cannabidiorcol) and enzymes mentioned above was obtained by various software programs including AutoDock Vina 4.2, AutoDock, and iGEMDOCK. In comparison to Donepezil (BA = -8.4 kcal/mol, Ki = 1.46 mM), Rivastigmine (BA = -7.0 kcal/mol, Ki = 0.02 mM), and Galantamine (BA = -7.1, Ki = 2.1 mM), Cannabidiorcol (BA = -9.4 kcal/mol, Ki = 4.61 mM) shows significant inhibition of AChE. On the other hand, Cannabinol C2 (BA = -9.2 kcal/mol, Ki = 4.32 mM) significantly inhibits Butyrylcholinesterase (BuChE) in comparison to Memantine (BA = -6.8 kcal/mol, Ki = 0.54 mM). This study sheds new light and opens new avenues for elucidating the role of bioactive compounds present in Cannabis sativa in treating Alzheimer's disease.

Mechanistic Insights and Potential Therapeutic Approaches in PolyQ Diseases via Autophagy.

Polyglutamine diseases are a group of congenital neurodegenerative diseases categorized with genomic abnormalities in the expansion of CAG triplet repeats in coding regions of specific disease-related genes. Protein aggregates are the toxic hallmark for polyQ diseases and initiate neuronal death. Autophagy is a catabolic process that aids in the removal of damaged organelles or toxic protein aggregates, a process required to maintain cellular homeostasis that has the potential to fight against neurodegenerative diseases, but this pathway gets affected under diseased conditions, as there is a direct impact on autophagy-related gene expression. The increase in the accumulation of autophagy vesicles reported in neurodegenerative diseases was due to an increase in autophagy or may have been due to a decrease in autophagy flux. These reports suggested that there is a contribution of autophagy in the pathology of diseases and regulation in the process of autophagy. It was demonstrated in various disease models of polyQ diseases that autophagy upregulation by using modulators can enhance the dissolution of toxic aggregates and delay disease progression. In this review, interaction of the autophagy pathway with polyQ diseases was analyzed, and a therapeutic approach with autophagy inducing drugs was established for disease pathogenesis.

Proteomic Approach for Comparative Analysis of the Spike Protein of SARS-CoV-2 Omicron (B.1.1.529) Variant and Other Pango Lineages.

The novel SARS-CoV-2 variant, Omicron (B.1.1.529), is being testified, and the WHO has characterized Omicron as a variant of concern due to its higher transmissibility and very contagious behavior, immunization breakthrough cases. Here, the comparative proteomic study has been conducted on spike-protein, hACE2 of five lineages (α, ß, δ, γ and Omicron. The docking was performed on spike protein- hACE-2 protein using HADDOCK, and PRODIGY was used to analyze the binding energy affinity using a reduced Haddock score. Followed by superimposition in different variant-based protein structures and calculated the esteem root mean square deviation (RMSD). This study reveals that Omicron was seen generating a monophyletic clade. Further, as α variant is the principal advanced strain after Wuhan SARS-CoV-2, and that is the reason it was showing the least likeness rate with the Omicron and connoting Omicron has developed of late with the extreme number of mutations. α variant has shown the highest binding affinity with hACE2, followed by ß strain, and followed with γ. Omicron showed a penultimate binding relationship, while the δ variant was seen as having the least binding affinity. This proteomic basis in silico analysis of variable spike proteins of variants will impart light on the development of vaccines and the identification of mutations occurring in the upcoming variants.