Summary

Neurodegeneration refers to the progressive loss of neuron structure or function, which may eventually lead to cell death. Many neurodegenerative diseases, such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington's disease and prion disease, are the results of neurodegenerative processes. Neurodegeneration can be found in many different levels of neuronal circuits in the brain, from molecules to systems. Since there is no known method to reverse the progressive degeneration of neurons, these diseases are considered incurable. Biomedical research has revealed many similarities between these diseases at the subcellular level, including atypical protein assembly (such as protein diseases) and induction of cell death. These similarities indicate that progress in the treatment of one neurodegenerative disease may also improve other diseases. This collection of entries aims to collect various medical research results related to neurodegeneration. We invite researchers to share their new results and ideas related to neurodegeneration.

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Entries
Topic Review
Microglial Potassium Channels: From Homeostasis to Neurodegeneration
The growing interest in the role of microglia in the progression of many neurodegenerative diseases is developing in an ever-expedited manner, in part thanks to emergent new tools for studying the morphological and functional features of the CNS. The discovery of specific biomarkers of the microglia phenotype could find application in a wide range of human diseases, and creates opportunities for the discovery and development of tailored therapeutic interventions. 
  • 534
  • 21 Dec 2021
Topic Review
Mitochondria, Neuroinflammatory and Neurodegenerative Diseases
Mitochondria are vital organelles in eukaryotic cells that control diverse physiological processes related to energy production, calcium homeostasis, the generation of reactive oxygen species, and cell death. Several studies have demonstrated that structural and functional mitochondrial disturbances are involved in the development of different neuroinflammatory (NI) and neurodegenerative (ND) diseases (NI&NDDs) such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis.
  • 389
  • 20 Dec 2021
Topic Review
G-Protein-Coupled Receptors (GPCRs)
Despite the identification of Aβ plaques and NFTs as biomarkers for Alzheimer’s disease (AD) pathology, therapeutic interventions remain elusive, with neither an absolute prophylactic nor a curative medication available to impede the progression of AD presently available. Current ap-proaches focus on symptomatic treatments to maintain AD patients’ mental stability and behav-ioral symptoms by decreasing neuronal degeneration; however, the complexity of AD patholo-gy requires a wide range of therapeutic approaches for both preventive and curative treatments. In this regard, this entry summarizes the role of receptors as a potential target for treating AD and focuses on the path of major receptors which are responsible for AD progression. This re-view gives an overall idea centering on major receptors, their agonist and antagonist and future prospects of viral mimicry in AD pathology. This entry aims to provide researchers and devel-opers a comprehensive idea about the different receptors involved in AD pathogenesis that may lead to finding a new therapeutic strategy to treat AD.
  • 762
  • 16 Dec 2021
Topic Review
Multiple Sclerosis Pathology--Potential Disease Biomarkers
Multiple sclerosis (MS) is a complex disease of the central nervous system (CNS) that involves an intricate and aberrant interaction of immune cells leading to inflammation, demyelination, and neurodegeneration. Due to the heterogeneity of clinical subtypes, their diagnosis becomes challenging and the best treatment cannot be easily provided to patients. Biomarkers have been used to simplify the diagnosis and prognosis of MS, as well as to evaluate the results of clinical treatments.
  • 549
  • 15 Dec 2021
Topic Review
Common Underlying Mechanisms of Multiple Sclerosis and Epilepsy
Despite the significant differences in the pathological background of neurodegenerative diseases, epileptic seizures are comorbidity in many disorders such as Huntington disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS). Regarding the last one, specifically, it has been shown that the risk of developing epilepsy is three to six times higher in patients with MS compared to the general population. In this context, understanding the pathological processes underlying this connection will allow for the targeting of the common and shared pathological pathways involved in both conditions, which may provide a new avenue in the management of neurological disorders.
  • 738
  • 15 Dec 2021
Topic Review
Reactive Oxygen Species-Induced mtDNA Release
One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis, is microglia-mediated and astrocyte-mediated neuroinflammation. Although inhibitions of both harmful proteins and aggregation are major treatments for neurodegenerative diseases, whether the phenomenon of non-normal protein or peptide aggregation is causally related to neuronal loss and synaptic damage is still controversial. Currently, excessive production of reactive oxygen species (ROS), which induces mitochondrial dysfunction in neurons that may play a key role in the regulation of immune cells, is proposed as a regulator in neurological disorders. In this review, we propose that mitochondrial DNA (mtDNA) release due to ROS may act on microglia and astrocytes adjacent to neurons to induce inflammation through activation of innate immune responses (such as cGAS/STING). Elucidating the relationship between mtDNA and the formation of a pro-inflammatory microenvironment could contribute to a better understanding of the mechanism of crosstalk between neuronal and peripheral immune cells and lead to the development of novel therapeutic approaches to neurodegenerative diseases.
  • 472
  • 17 Dec 2021
Topic Review
Primary Human Trabecular Meshwork Model for Pseudoexfoliation
Pseudoexfoliation is an age related fibrillopathy characterized by abnormal fibrillar extracellular material (ECM) in ocular tissues. Pseudoexfoliative aggregate material causing mechanical obstruction of the trabecular meshwork (TM), blood aqueous barrier dysfunction, endothelial cell dysfunction, and abnormal ECM homeostasis cause TM dysfunction/fibrosis eventually leading to glaucoma, if untreated. The pseudoexfoliative material comprises of non-collagenous basement membrane components such as laminin, fibronectin, amyloid P, and vitronectin as well as proteinaceous components of elastic fibres (such as elastin, tropoelastin, fibrillin-1, microfibril-associated glycoprotein-1) and latent TGF-β-binding proteins (LTBP-1 and -2). Transforming growth factor, tissue matrix metalloproteinases (MMPs) and plasminogen activator inhibitor-1 (PAI-1) regulate ECM homeostasis with increased PAI-1 levels causing excessive ECM deposition and reduced degradation in adjoining tissues. While Lysyl oxidase homolog 1 (LOXL1) is deemed necessary for disease pathogenesis, it is now understood that LOXL1 alone does not explain the preferential geographical distribution or the differential role of different genes in disease pathogenesis or glaucoma onset in different ethnic populations. It is well recognized that environmental factors, epigenetics, and their interplay with gene expression is what may hold the key for explaining the disease pathogenesis.
  • 366
  • 14 Dec 2021
Topic Review
Ischemic Stroke and Excitotoxicity
Stroke is a relevant cause of death, disability and dementia worldwide. In ischemic stroke, excitotoxicity is the main mechanism of neuronal death in the penumbra area, a potentially recoverable tissue surrounding the irreversibly damaged infarct core. In excitatory neurons, scaffold protein PSD-95 plays a central role in neuronal function but also survival/death choices. Thus, this protein is a promising target for development of neuroprotective strategies for stroke and other pathologies similarly associated to excitotoxicity.
  • 466
  • 13 Dec 2021
Topic Review
Role of TCA Cycle-Related Enzymes in Human Diseases
The tricarboxylic acid (TCA) cycle, also known as the citrate acid cycle, is a series of chemical reactions to form energy required for cellular function through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. There are eight enzymes in the TCA cycle that oxidize acetyl-coenzyme A (acetyl-CoA), and genetic or non-genetic alterations in these enzymes are closely associated with human diseases, especially cancer and neurodegeneration, but the role of these eight enzymes remains unclear.
  • 948
  • 09 Dec 2021
Topic Review
MicroRNA-Target Interaction Regulatory Network
Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia; however, early diagnosis of the disease is challenging. Research suggests that biomarkers found in blood, such as microRNAs (miRNA), may be promising for AD diagnostics. Experimental data on miRNA–target interactions (MTI) associated with AD are scattered across databases and publications, thus making the identification of promising miRNA biomarkers for AD difficult. In response to this, a list of experimentally validated AD-associated MTIs was obtained from miRTarBase. Cytoscape was used to create a visual MTI network. STRING software was used for protein–protein interaction analysis and mirPath was used for pathway enrichment analysis. Several targets regulated by multiple miRNAs were identified, including: BACE1, APP, NCSTN, SP1, SIRT1, and PTEN. The miRNA with the highest numbers of interactions in the network were: miR-9, miR-16, miR-34a, miR-106a, miR-107, miR-125b, miR-146, and miR-181c. The analysis revealed seven subnetworks, representing disease modules which have a potential for further biomarker development. The obtained MTI network is not yet complete, and additional studies are needed for the comprehensive understanding of the AD-associated miRNA targetome. 
  • 415
  • 08 Dec 2021
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