Download Free Development Of Small Molecules For Disrupting Pathological Amyloid Aggregation In Neurodegenerative Diseases Book in PDF and EPUB Free Download. You can read online Development Of Small Molecules For Disrupting Pathological Amyloid Aggregation In Neurodegenerative Diseases and write the review.

Neurodegenerative diseases (NDs), encompassing Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), are often characterized by the formation of pathological amyloid aggregates, predominantly composed of proteins like amyloid-β, tau, α-synuclein, TDP-43, and others. These amyloid aggregates inflict significant neuronal harm and incite inflammation. This review underscores the potential of small molecules as innovative therapeutic interventions, designed to influence the formation, stability, and breakdown of these pathological amyloid aggregates, which could potentially modify the disease’s progression and minimize its neurotoxic effects. This review first sketches the pathways and mechanisms involved in amyloid aggregation, followed by an in-depth analysis of recent advances in formulating small molecules that directly target these damaging aggregates. This includes various strategies such as inhibiting fibril formation, fostering off-pathway non-toxic oligomers or amorphous aggregates, disaggregating established pathological amyloid fibrils, and enhancing the protein quality control system to combat amyloid aggregation. In the end, this review identifies the challenges and opportunities involved in transitioning these molecules into effective treatments, focusing on critical factors such as penetration of the blood-brain barrier, target specificity, and safety considerations. This review, thus, presents a comprehensive overview of the potential role of small molecules in tackling NDs typified by amyloid aggregation.
Biological Soft Matter Explore a comprehensive, one-stop reference on biological soft matter written and edited by leading voices in the field Biological Soft Matter: Fundamentals, Properties and Applications delivers a unique and indispensable compilation of up-to-date knowledge and material on biological soft matter. The book presents a thorough overview about biological soft matter, beginning with different substance classes, including proteins, nucleic acids, lipids, and polysaccharides. It goes on to describe a variety of superstructures and aggregated and how they are formed by self-assembly processes like protein folding or crystallization. The distinguished editors have included materials with a special emphasis on macromolecular assembly, including how it applies to lipid membranes, and proteins fibrillization. Biological Soft Matter is a crucial resource for anyone working in the field, compiling information about all important substance classes and their respective roles in forming superstructures. The book is ideal for beginners and experts alike and makes the perfect guide for chemists, physicists, and life scientists with an interest in the area. Readers will also benefit from the inclusion of: An introduction to DNA nano-engineering and DNA-driven nanoparticle assembly Explorations of polysaccharides and glycoproteins, engineered biopolymers, and engineered hydrogels Discussions of macromolecular assemblies, including liquid membranes and small molecule inhibitors for amyloid aggregation A treatment of inorganic nanomaterials as promoters and inhibitors of amyloid fibril formation An examination of a wide variety of natural and artificial polymers Perfect for materials scientists, biochemists, polymer chemists, and protein chemists, Biological Soft Matter: Fundamentals, Properties and Applications will also earn a place in the libraries of biophysicists and physical chemists seeking a one-stop reference summarizing the rapidly evolving topic of biological soft matter.
Neurofibrillary tangles (NFTs) composed of intracellular aggregates of tau protein are a key neuropathological feature of Alzheimer’s Disease (AD) and other neurodegenerative diseases, collectively termed tauopathies. The abundance of NFTs has been reported to correlate positively with the severity of cognitive impairment in AD. However, accumulating evidences derived from studies of experimental models have identified that NFTs themselves may not be neurotoxic. Now, many of tau researchers are seeking a “toxic” form of tau protein. Moreover, it was suggested that a “toxic” tau was capable to seed aggregation of native tau protein and to propagate in a prion-like manner. However, the exact neurotoxic tau species remain unclear. Because mature tangles seem to be non-toxic component, “tau oligomers” as the candidate of “toxic” tau have been investigated for more than one decade. In this topic, we will discuss our consensus of “tau oligomers” because the term of “tau oligomers” [e.g. dimer (disulfide bond-dependent or independent), multimer (more than dimer), granular (definition by EM or AFM) and maybe small filamentous aggregates] has been used by each researchers definition. From a biochemical point of view, tau protein has several unique characteristics such as natively unfolded conformation, thermo-stability, acid-stability, and capability of post-translational modifications. Although tau protein research has been continued for a long time, we are still missing the mechanisms of NFT formation. It is unclear how the conversion is occurred from natively unfolded protein to abnormally mis-folded protein. It remains unknown how tau protein can be formed filaments [e.g. paired helical filament (PHF), straight filament and twisted filament] in cells albeit in vitro studies confirmed tau self-assembly by several inducing factors. Researchers are still debating whether tau oligomerization is primary event rather than tau phosphorylation in the tau pathogenesis. Inhibition of either tau phosphorylation or aggregation has been investigated for the prevention of tauopathies, however, it will make an irrelevant result if we don’t know an exact target of neurotoxicity. It is a time to have a consensus of definition, terminology and methodology for the identification of “tau oligomers”.
This book will focus on synthesis, coating and functionalization chemistry of selected nanoparticles that are most commonly used in various biomedical applications. Apart from standard selected chemical synthetic methods, it focusses on design consideration of functionalization, selected coating chemistry for transforming as synthesized nanoparticle, selected conjugation chemistries and purification approach for such nanoparticles. It also includes state-of-art/future prospect of nanodrugs suitable for clinical applications. There will material on general application potential of these nanoparticles, importance of functionalization and common problems faced by non-chemists.
Cyclin Dependent Kinase 5 provides a comprehensive and up-to-date collection of reviews on the discovery, signaling mechanisms and functions of Cdk5, as well as the potential implication of Cdk5 in the treatment of neurodegenerative diseases. Since the identification of this unique member of the Cdk family, Cdk5 has emerged as one of the most important signal transduction mediators in the development, maintenance and fine-tuning of neuronal functions and networking. Further studies have revealed that Cdk5 is also associated with the regulation of neuronal survival during both developmental stages and in neurodegenerative diseases. These observations indicate that precise control of Cdk5 is essential for the regulation of neuronal survival. The pivotal role Cdk5 appears to play in both the regulation of neuronal survival and synaptic functions thus raises the interesting possibility that Cdk5 inhibitors may serve as therapeutic treatment for a number of neurodegenerative diseases.
The editor of this volume, having research interests in the field of ROS production and the damage to cellular systems, has identified a number of enzymes showing ·OH scavenging activities details of which are anticipated to be published in the near future as confirmatory experiments are awaited. It is hoped that the information presented in this book on NDs will stimulate both expert and novice researchers in the field with excellent overviews of the current status of research and pointers to future research goals. Clinicians, nurses as well as families and caregivers should also benefit from the material presented in handling and treating their specialised cases. Also the insights gained should be valuable for further understanding of the diseases at molecular levels and should lead to development of new biomarkers, novel diagnostic tools and more effective therapeutic drugs to treat the clinical problems raised by these devastating diseases.
This book is aimed at generating an updated reservoir of scientific endeavors undertaken to unravel the complicated yet intriguing topic of neurodegeneration. Scientists from Europe, USA and India who are experts in the field of neurodegenerative diseases have contributed to this book. This book will help readers gain insight into the recent knowledge obtained from Drosophila model, in understanding the molecular mechanisms underlying neurodegenerative disorders and also unravel novel scopes for therapeutic interventions. Different methodologies available to create humanized fly models that faithfully reflects the pathogenicities associated with particular disorders have been described here. It also includes information on the exciting area of neural stem cells. A brief discussion on neurofibrillary tangles, precedes the elaborate description of lessons learnt from Drosophila about Alzheimer's, Parkinson’s, Spinomuscular Atrophy, Huntington’s diseases, RNA expansion disorders and Hereditary Spastic Paraplegia. We have concluded the book with the use of Drosophila for identifying pharmacological therapies for neurodegenerative disorders. The wide range of topics covered here will not only be relevant for beginners who are new to the concept of the extensive utility of Drosophila as a model to study human disorders; but will also be an important contribution to the scientific community, with an insight into the paradigm shift in our understanding of neurodegenerative disorders. Completed with informative tables and communicative illustrations this book will keep the readers glued and intrigued. We have comprehensively anthologized the lessons learnt on neurodegeneration from Drosophila and have thus provided an insight into the multidimensional aspects of pathogenicities of majority of the neurodegenerative disorders.
This comprehensive reference provides a detailed overview of current concepts regarding the cause of Parkinson's disease-emphasizing the issues involved in the design, implementation, and analysis of epidemiological studies of parkinsonism.
Up-to-date discussion of the etiology, diagnosis, treatment, and prevention of this common cause of stroke and cognitive impairment.