Redox homeostasis results from the balance between the production of reactive species (e.g. ROS, RNS, etc) and their detoxification by endogenous or exogenous antioxidants. ROS play several important physiological roles, however, their excessive production or impaired detoxification is associated with oxidative stress and cellular injury. Importantly, oxidative damage to vulnerable central nervous system (CNS) cells is a common pathological feature of several neurodegenerative diseases. Antioxidants have been considered as attractive potential therapeutic agents to prevent or halt disease progression but the clinical efficacy of antioxidant treatment strategies is still marginal. Improvement of antioxidant therapy effectiveness might involve adjustment of preclinical to clinical settings and development of new efficient delivery methods and will require a more in-depth knowledge of cellular redox-signaling mechanisms. Promising novel redox-based therapeutic strategies are gaining relevance to combat oxidative stress associated with neurodegenerative diseases. These include boosting the endogenous antioxidant machinery through activation of the antioxidant master regulator Nrf2 (nuclear factor erythroid 2-related factor 2) or modulation of ROS production by NOX (nicotinamide adenine dinucleotide phosphate (NADPH) oxidase) inhibitors. Redox regulation of key cellular functions is currently recognized as an important cellular signaling mechanism and events such as post-translational modifications (e.g. S_glutathionylation, S_nitrosylation, glycosylation, etc) play important roles in redox signal transduction and might be instrumental to uncover pathological mechanisms and identify novel therapeutic targets in neurodegenerative diseases. This Research Topic focuses on redox signaling mechanisms and aims to provide novel insights into the role of redox-signaling, with particular emphasis on redox regulation involving post-translational modifications, in the pathophysiology of neurodegenerative diseases. Moreover, it aims to present an overview of the potential of antioxidants as therapeutics for CNS disorders with a special focus on emerging novel therapeutic redox-based strategies. We are particularly interested in studies: -addressing new redox-based molecular mechanisms contributing to neurodegenerative diseases; -exploring the role of naturally occurring compounds, standard medications, and nutraceuticals with antioxidant properties in modulating redox-signaling pathways and limiting and/or preventing oxidative damage associated with these disorders; -addressing mechanistically the role of post-translational modifications in the pathophysiology of neurodegenerative disorders.

This book aims to present the age-related alterations in redox signaling networks and their diagnostic biomarkers in aging cells using multidisciplinary approach. Establishing sensitive and specific biomarkers of dynamic redox homeostasis is crucially important in the development of effective antiaging and senolytic interventions. Recent years have seen tremendous advances in the understanding of redox signaling events which highlight the process of aging and age-related pathologies. A major challenge in biological aging research is developing reliable biomarkers to determine the consequences of disrupted redox signaling networks long before the clinical diagnosis of age-related diseases is made. Therefore, we have chosen to concentrate on aging-induced aberrant redox signaling networks, their biomarkers, and pathological consequences in this book. Although oxidation is a natural metabolic process, the imbalance in the level of oxidants and antioxidants causes oxidative stress and eventually leads to inflammatory conditions, diabetes, neurodegenerative diseases, and cancer. Novel redox-sensitive biomarkers for the evaluation of aging-induced proteinopathies such as amyloid ß and tau proteins in Alzheimer's disease, α-synuclein in Parkinson's disease, and islet amyloid polypeptides in type 2 diabetes mellitus recently drew the attention of researchers. Inside this textbook, readers will find comprehensive perspectives on the association between redox homeostasis and the aging process both at the molecular and clinical levels. Due to the inherent relationship between impaired metabolic activities and oxidative stress, the temporal interaction between intermediary metabolism and disturbed redox status can lead to greater susceptibility to aging-induced diseases and disorders, such as cardiovascular diseases, hypertension, and diabetes. This knowledge could be a key to continued research toward improving medication regimens such as in cancer and cardiovascular therapies, and procedural outcomes for patients. This book brings together current research evidence and knowledge on redox signaling and biomarkers in aging in chapters written by leading global experts in this rapidly evolving field. We hope that this textbook is of interest to a wide group of researchers, advanced students, scientifically curious non-specialist readers and clinicians alike.

The Charnolosome as a Novel Nanothereranostic Biomarker: Overcoming Future Challenges in Medicine provides an overview of the charnolosome and its potential as a biomarker of cell injury. Based on the author's original discovery of the charnoly body in the developing, undernourished rat cerebellar Purkinje neurons, this book delves into the potential for utilizing this mitochondria and lysosomal-derived intracellular organelle as a nanotheranostic biomarker to prevent and cure various diseases. The book discusses the cellular, molecular, genetic, and epigenetic mechanisms of charnolosomes and charnolosome-derived nano-vesicles. It also investigates the molecular mechanisms underlying auto-inflammatory, autoimmune, and infectious diseases resulting from their compromised mitochondrial bioenergetics, and the potential use of the charnolosome in preventing and curing such conditions. - Shares the latest knowledge on the charnolosome and charnolosome-derived nano-vesicles and their significance at a cellular and molecular level - Considers the charnolosome in relation to a range of conditions, including neurodegenerative, metabolic, and multi-drug resistant systemic diseases - Presents future perspectives of the charnolosome in personalized nanotheranostics

Neurodegenerative diseases are debilitating disorders defined as loss of function or progressive destructing structure of the nervous system with high prevalence among the aging population. These diseases mainly include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS). They are significantly associated with age and degeneration, becoming a devastating global health issue as a result of the growth of mean life expectancy worldwide. Few or no effective treatments are available for age-related neurodegenerative diseases, causing large socioeconomic and personal costs. The last 15 years have seen a boom in the use and integration of “omic” approaches (such as genomic, transcriptomic, epigenomic and metabolomic techniques) to study neurodegenerative disease in an unprecedented way. While, to date, no therapy based on these approaches is available to cure neurodegenerative diseases. Therefore, it is necessary to search for new, safe, and effective drug candidates and treatment strategies. In this Research Topic, our prime focus would be on the use and integration of “omic” approaches to study biomarkers, pathogenesis, disease progression and new therapeutic target of neurodegenerative diseases, so as to search for new, safe, and effective drug candidates.

This new volume, a part of the Proteomics, Metabolomics, Interactomics and Systems Biology series, will explain how proteomic studies of post-translational modifications (PTMs) can be applied to neurodegenerative diseases and relevant studies. The goal of the book is to increase awareness among researchers about how PTMs may be helpful in understanding mechanisms in various neurodegenerative diseases through proteomic studies. This book will serve as a tool for those who want to begin work in the proteomics field and explore how to implement PTMs studies into their work. Chapter authors will describe different PTMs enrichment methods developed by experts in the field so that researchers may learn to apply these methods and techniques to new studies. Divided into three sections, chapters will cover sample preparation, data quality, enrichment techniques, guidelines on how to analyze PTMs, and explain the role of PTMs and different brain diseases. Among those topics includes will be brain cancer, SLA disease, Parkinsons disease, muscular dystrophies, and schizophrenia. This volume will be useful for researchers and students studying brain and neurodegenerative diseases who are interested in delving into work with proteomic studies and PTMs.

Diversified physicochemical injuries trigger Charnoly body (CB) formation as pleomorphic, electron-dense, multi-lamellar stacks of nonfunctional mitochondrial membranes in the most vulnerable cell. Free radicals induce downregulation of mitochondrial DNA, microRNA, AgNOR, and epigenetics to trigger CB molecular pathogenesis. CB is eliminated by energy (ATP)-driven lysosome-dependent charnolophagy as a basic molecular mechanism of intracellular detoxification to prevent acute and chronic diseases. Accumulation of CB at the junction of axon hillock and charnolosome (CS) at the synapses causes cognitive impairments; whereas, nonspecific induction of CB causes GIT stress, myelosuppression, alopecia, neurotoxicity, cardiotoxicity, and infertility in multidrug-resistant malignancies. Hence, stem cell-specific CB, charnolophagy, and CS agonists/antagonists are introduced as novel charnolopharmacotherapeutics for the successful treatment of cardiovascular diseases, neurodegenerative diseases, infectious diseases, drug addiction, and cancer. Nanoparticles to improve drug delivery, CS exocytosis, and disease-specific spatiotemporal charnolosomics employing correlative and combinatorial bioinformatics boost mitochondrial bioenergetics through balanced diet, exercise, and antioxidants. The book will be of interest to medical scientists and practitioners.

Phospholipases in Physiology and Pathology presents a comprehensive overview on the physiology and pathology of phospholipases. This seven-volume set considers the biochemical and molecular mechanisms of normal and abnormal cell function upon dysregulation of phospholipases in different diseases. Volumes cover signal transduction mechanisms, implications in cancer, infectious diseases, neural diseases, cardiovascular diseases and other diseases, implications in inflammation, apoptosis, gene expression and non-coding RNAs, the role of natural and synthetic compounds, and stem cell therapies, nanotechnology-based therapies, and more. Together, these volumes give researchers critical insight on the mechanistic and therapeutic aspects of phospholipases. Discusses the biochemical and molecular mechanisms of normal and abnormal cell function in different disease processes Covers a wide range of basic and translational research appropriate for scientists engaged in studying the regulation of phospholipases from interdisciplinary perspectives Features state-of-the-art chapter contributions from international leaders in the field

Molecular Targets of CNS Tumors is a selected review of Central Nervous System (CNS) tumors with particular emphasis on signaling pathway of the most common CNS tumor types. To develop drugs which specifically attack the cancer cells requires an understanding of the distinct characteristics of those cells. Additional detailed information is provided on selected signal pathways in CNS tumors.

Some mild stresses have positive effects on survival and aging as shown in animal models. There is also a large body of research that demonstrates these hormetic effects on aging, health, and resistance to severe stresses and diseases in human beings. However, the data are dispersed in the literature and are not always interpreted as hormetic effec