Microglia represent the first line of immune feedback in the brain. Beyond immune surveillance, they are essential for maintaining brain homeostasis. Recent research has revealed the microglial cells' spatiotemporal heterogeneity based on their local and time-based functions in brain trauma or disease when homeostasis is disrupted. Distinct "microglial signatures" have been recorded in physiological states and brain injuries, with discrete or sometimes overlapping pro- and anti-inflammatory functions. Microglia are involved in the neurological repair processes, such as neurovascular unit restoration and synaptic plasticity, and manage the extent of the damage due to their phenotype switching. The versatility of cellular phenotypes beyond the classical M1/M2 classification, as well as the double-edge actions of microglia in neurodegeneration, indicate the need for further exploration of microglial cell dynamics and their contribution to neurodegenerative processes. This review discusses the homeostatic functions of different microglial subsets focusing on neuropathological conditions. Also, we address the feasibility of targeting microglia as a therapeutic strategy in neurodegenerative diseases.
Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disorder worldwide. In ALS, progressing disease can result from misfolding and aggregation of superoxide dismutase‐1 (SOD1) or TAR DNA‐binding protein 43 kDa (TDP43). An efficient immunotherapy for ALS should spare intact SOD1 while eliminating its dysfunctional variant. We utilized advanced immunoinformatics to suggest a potential vaccine candidate against ALS by proposing a model of dynamic TLR4 mediation and induction of a specific Th2‐biased shift against mutant SOD1, TDP43, and TRAF6, a protein that specifically interacts with dysfunctional SOD1. SOD1, TDP43, and TRAF6 were retrieved in FASTA. Immune Epitopes Database and CTLpred suggested T/B‐cell epitopes from disease‐specific regions of selected antigens. A TLR4‐mediating adjuvant, RS01, was used. Sequences were assembled via suitable linkers. Tertiary structure of the protein was calculated. Refined protein structure and physicochemical features of the 3D structure were verified in silico. Differential immune induction was assessed via C‐ImmSim. GROningen MAchine for Chemical Simulation was used to assess evolution of the docked vaccine–TLR4 complex in blood. Our protein showed high structural quality and was nonallergenic and immune inducing. Also, the vaccine–TLR4 complex stability was verified by RMSD, RMSF, gyration, and visual analyses of the molecular dynamic trajectory. Contact residues in the vaccine–TLR4 complex showed favorable binding energies. Immune stimulation analyses of the proposed candidate demonstrated a sustained memory cell response and a strong adaptive immune reaction. We proposed a potential vaccine candidate against ALS and verified its physicochemical and immune inducing features. Future studies should assess this vaccine in animal studies.
Context: Despite major advancements in the field, the current neurosurgical practice requires an interdisciplinary approach. It is known that surgical practice and other cancer-eliminating treatments can be combined for optimal results. However, recent attempts have failed to address many debilitating conditions, indicating an emergent need for novel interdisciplinary therapeutic approaches. Evidence Acquisition: We searched PubMed and Google Scholar for the keywords “immunoinformatics,” “in silico,” “neurology,” and “neurosurgery.” Without time restriction. Results: The immune system is versatile because it is involved in physiological brain function and affects the course of central nervous system (CNS) disease and infection. A novel approach combines neurosurgery and immunoinformatics for optimal results. For instance, brain tumors, such as glioblastoma multiforme (GBM), are still associated with a severely reduced survival of patients, and resection of tumors may provide little help. In silico approaches could help to identify molecular pathways and design immunotherapies for such conditions at a significantly increased speed compared to traditional vaccinology approaches. Conclusions: The neurosurgical practice could be affected by different infectious organisms. These organisms can be targeted by in silico vaccinology techniques. Here, we provide a brief overview of bioinformatics/immunoinformatics and discuss the possible role of immunoinformatics in neurosurgery. In light of the current Coronavirus disease-2019 (COVID-19) epidemic, projections for future studies are also included.
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