This book describes the latest research on neurodegenerative disease and metal-binding proteins. It lays strong emphasis on biochemistry and cell biology. The diseases covered in the book include Parkinson's disease, Alzheimer's disease, prion disease, and ALS. The chapters separately examine such issues as mechanisms of metal binding, metal-induce

Biometals in Neurodegenerative Diseases: Mechanisms and Therapeutics is an authoritative and timely resource bringing together the major findings in the field for ease of access to those working in the field or with an interest in metals and their role in brain function, disease, and as therapeutic targets. Chapters cover metals in Alzheimer’s Disease, Parkinson’s Disease, Motor Neuron Disease, Autism and lysosomal storage disorders. This book is written for academic researchers, clinicians and advanced graduate students studying or treating patients in neurodegeneration, neurochemistry, neurology and neurotoxicology. The scientific literature in this field is advancing rapidly, with approximately 300 publications per year adding to our knowledge of how biometals contribute to neurodegenerative diseases. Despite this rapid increase in our understanding of biometals in brain disease, the fields of biomedicine and neuroscience have often overlooked this information. The need to bring the research on biometals in neurodegeneration to the forefront of biomedical research is essential in order to understand neurodegenerative disease processes and develop effective therapeutics. Authoritative and timely resource bringing together the major findings in the field for those with an interest in metals and their role in the brain function, disease, and as therapeutic targets Written for academic researchers, clinicians, and advanced graduate students studying, or treating, patients in neurodegeneration, neurochemistry, neurology and neurotoxicology Edited by international leaders in the field who have contributed greatly to the study of metals in neurodegenerative diseases

Metalloproteins and Motor Proteins, Volume 141 focuses on recent advances in studying metalloproteins and motor proteins, along with their roles in different pathologies and drug-resistance. Chapters include Transcriptomic Analysis Reveals Zinc-Mediated Virulence and Pathogenicity in Multidrug-Resistant Acinetobacter baumannii, The Mechanistic Insights into Different Aspects of Promiscuity in Metalloenzymes, Role of Metal ion in ion channel Mechanisms, A model of microtubule depolymerization by kinesin-8 motor proteins, Metalloproteins and metalloproteomics in health and disease, Decoding Genetic and Pathophysiological Mechanisms in Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis: A Comparative Study of Differentially Expressed Genes and Implicated Pathways in Motor Neuron Disorders, and much more. Additional chapters cover Exploring the effect of disease causing mutations in metal binding sites of human ARSA in Metachromatic Leukodystrophy, Role of transmembrane proteins in regulating metalloproteins and motor proteins in human cancer, Role of transmembrane proteins in metalloproteins and motor proteinsin human neurogenesis, Role of transmembrane proteins in metalloproteins and motor proteins in human aging, Vesicle transport of metalloproteinases, Motor proteins and spermatogenesis, and much more. Integrates experimental and computational methods for studying structure and function of metalloproteins and motor proteins and their implication in drug design Presents timely chapters written by well-renowned authorities in their field Contains a high number of high quality illustrations, figures, and tables and targets a very wide audience of specialists, researchers, and students

This book covers the new Omics area, Metallomics. As Metallomics is intrinsically a transdisciplinary area, this book is authored by experts in the field on such diverse topics as Environmental, Nuclear, and Human Metallomics. Within these topics metals play important role, as being part of biomolecules, controlling different biochemical process, being signaling agents, being catalyst of biochemical reactions, among others. This volume demonstrates the importance of more investigation about metals and their interactions with biomolecules. As the knowledge in this field is growing and growing daily, then new challenges concerning studies involving Metallomics is appearing, such as comparative metallomics, speciation metallomics, real-time metallomics, new predictions of metals in biomolecules, metalloprotein databank expansion, interactions between metalloprotein-metalloprotein, among others.

Vols. for 1963- include as pt. 2 of the Jan. issue: Medical subject headings.

This book illustrates the importance of natural products as the source for the development of novel drugs for the treatment of neurodegenerative disorders, including Alzheimer's disease. It also highlights the role of reactive oxygen species and altered metal homeostasis in the progression of Alzheimer’s disease and examines the potential of antioxidants and anti-chelating agents in the clinical intervention of neurodegenerative diseases. The book also discusses the role of neuroinflammation in the pathogenesis of Alzheimer’s disease. The chapters provide information about the drug targets, progress in the development of natural product-based therapeutics, biomarkers, fluorescent diagnostic tools, and theranostic for Alzheimer's disease. The book also provides information about the design and synthesis of natural product-based derivatives against the various targets of Alzheimer's disease including epigenetic targets and the metal dyshomeostasis hypothesis. Cutting across different disciplines, this book is a valuable source for neuroscientists, chemical biologists, pharmaceutical researchers, and synthetic biologists.

Several pathogenic mechanisms are involved in the pathogenesis of Parkinson’s Disease (PD), a neurodegenerative disease characterized by the loss of substantial nigra (SN) dopamine (DA) neurons. Alterations in calcium (Ca2+) homeostasis, cellular proteostasis, axonal transport, mitochondrial function, and neuroinflammation are linked to PD. However, research involving inter-organelle communication and their significance as precise mechanisms underlying neuronal death in PD remain to be elucidated. Evidence showed that perturbations in the mitochondria-endoplasmic reticulum (ER) network play an important role in the pathogenesis of PD. Alterations in the mitochondria-ER interface have been reported in PARK2 knockout mice and patients harboring PARK2 mutations. Enhanced parkin levels maintain mitochondria-ER cross-talk and assure regulated Ca2+ transfer to sustain cell bioenergetics. Several familial PD-related proteins, including Parkin and PINK1, may lead to modifications in the mitochondria-ER signaling. Interestingly, mitochondria-ER tethering suppresses mitophagy and parkin/PINK1-dependent mechanism regulates the destruction of mitochondria-ER contact sites by catalyzing a rapid burst of Mfn2 phospho-ubiquitination to trigger p97-dependent disassembly of Mfn2 complexes from the outer mitochondrial membrane. Mitofusin-mediated ER stress elicited neurodegeneration in Pink1/Parkin models of PD. α-Synuclein, a presynaptic protein, can bind to the ER-mitochondria tethering protein vesicle-associated membrane protein-associated protein B (VAPB) to disrupt Ca2+ homeostasis and mitochondrial ATP production. It has been reported that ER stress and mitochondrial cell death pathways might mediate A53T mutant α-synuclein-induced toxicity. Mitochondria-ER signaling mechanism is poorly characterized in neurons and its association in neuronal pathophysiology remains uncertain. The presence of mitochondria-ER contacts in neurons, preferentially at synapses, suggests a potential role in regulating synaptic activity. Alterations in mitochondria-ER associations are expected to be potentially detrimental to neurons, especially to SN DA neurons. Compounds from an unbiased chemical screen reverse both ER-to-Golgi trafficking defects and associated mitochondrial dysfunction in different PD models. In addition, a dibenzoylmethane derivative protects DA neurons against ER stress. Thus, mitochondria-ER signaling may represent a possible upstream drug target as potential therapeutic strategy for PD. In this Research Topic, we bring together knowledge that emphasizes the importance of mitochondria-ER communication and its impact to further dissect the pathogenic mechanisms in PD.