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Human Caspases And Neuronal Apoptosis In Neurodegenerative Diseases

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Human Caspases and Neuronal Apoptosis in Neurodegenerative Diseases

Human Caspases and Neuronal Apoptosis in Neurodegenerative Diseases Book
Author : Anil Gupta
Publisher : Academic Press
Release : 2021-12-17
ISBN : 0128204435
Language : En, Es, Fr & De

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Book Description :

Human Caspases and Neuronal Apoptosis in Neurodegenerative Diseases elucidates elaborately the role of caspase enzymes implicated in the initiation of molecular events leading to neuronal apoptosis in the neurodegenerative disease. The book starts with introduction to neuropathology, neurogenetics, and epidemiology of neurodegenerative disease and illustrates the involvement of human caspases, neuronal apoptosis, apoptotic pathways, genetic polymorphisms, and several other factors and underlying mechanisms in the pathology of Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. An important focus in all chapters is the intricate mechanisms and interplay that occur during or leading to neuron death in neurodegenerative diseases, along with disease pathobiology. Provides in-depth knowledge about neurotoxic potential of transition metals, impaired mitochondrial dynamics in the brain neurons, mutant proteins Aß peptide, tau protein, a-synuclein, huntingtin protein and formation of Lewy bodies, reactive oxygen and nitrogen species, ubiquitin proteasome dysregulation, and many others in neurodegenerative diseases Elucidates neurogenetics of gene APP, gene PSEN1, gene APOE, gene LRRK2, gene DJ1, and others in the pathology of neurodegenerative diseases. Explains caspases-mediated neuronal apoptosis in pathogenesis of Alzheimer’s disease covering amyloidogenesis, caspase-activated DNase, rho-associated coiled coil–containing protein kinase 1, mammalian sterile 20-like kinase 1, role of synaptic loss, microglial TREM2 receptor, microglial LRP1 receptor, microglial advanced glycation end-product receptor, astrocytic glial a 7 subtypes of nAChR, NLRP3 inflammasome, P2X purinoreceptors, miRNAs, and many other factors Demonstrates the role of caspases and apoptosis in Parkinson’s disease covering truncation of a-synuclein, neuroinflammation, parkin protein, activation of microglial cells, extrinsic and intrinsic pathways of apoptosis, ?tau314, and several other factors Explains etiopathogenesis of Huntington’s disease through covering clinically important topics as role of exon 1 HTT protein, ubiquitous nature of huntingtin, length of expanded polyglutamine tract, classically and alternately activated microglia, nuclear factor kappa B, kynurenine signaling pathway, tumor suppressor protein, PGC-1a gene, advanced glycation end-products, autophagy, and many other significant topics.

Targeting the Signalling Cascades Responsible for Human Neuronal Apoptosis Elicited by the Lipid Neuromodulator Platelet Activating Factor

Targeting the Signalling Cascades Responsible for Human Neuronal Apoptosis Elicited by the Lipid Neuromodulator Platelet Activating Factor Book
Author : Tia Corinne Moffat
Publisher : Unknown
Release : 2007
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Apoptosis is known to underlie neuronal loss in many human neurodegenerative disorders, such as Alzheimer disease (AD), HIV-dementia and ischemic stroke. Phospholipid signalling is involved in each of these conditions; changes in phospholipid membrane composition and phospholipid synthesis enzyme activity occurs in AD, while in HIV-dementia and ischemia there is an increased production and accumulation of inflammatory bioactive phospholipid mediators. Pathophysiological exposure to the phospholipid neuromodulator platelet activating factor (PAF) can initiate apoptotic pathways, and has been hypothesized to be a key mediator of neuronal death in these neurodegenerative disorders. It has been assumed that PAF signals exclusively through its G-protein coupled receptor (PAFR). However, our laboratory has shown that PAF can also induce apoptosis independently of PAFR and that ectopic expression of PAFR renders cells resistant to PAF-induced toxicity. This is relevant to neurodegenerative disease since PAFR expression in the human brain is found predominantly in non-neuronal cells suggesting that PAFR-independent signalling is also involved in neurodegeneration. This thesis focused on elucidating the PAF-induced, PAFR-independent apoptotic pathways in human neurons with the overarching goal of identifying new therapeutic targets capable of inhibiting neuronal loss in neurodegenerative disease. Here, PAF is shown to induce endoplasmic reticulum (ER) stress resulting in caspase-2 activation, leading to the activation of caspase-7, and culminating in DNA fragmentation in human neurons (hNTs) lacking PAFR. Mitochondrial effects, specifically release of cytochrome c from the mitochondria, caspase-9 activation, reactive oxygen species (ROS) production, and mitochondrial uncoupling protein-2 (UCP2) upregulation were initiated downstream of this primary ER cascade. To target this pathway, a panel of natural and synthetic compounds was screened for their ability to protect hNTs from neurotoxicity initiated by PAF and by the AD-related neurotoxic peptide amyloid-beta 1-42 (Abeta). Several compounds were identified as PAF/Abeta inhibitors. One of these compounds, nelfinavir (NFV), was tested for in vivo efficiency using the middle cerebral artery occlusion (MCAO) model of focal ischemia. NFV reduced infarct size, prevented neuronal apoptotic-like death, and improved behavioural recovery, solidifying the relation between PAF, AD, HIV-dementia, and ischemia-induced neuronal apoptosis. Together, these studies demonstrate that PAF can trigger neuronal apoptosis independently of PAFR, that inhibiting PAF-mediated pathways of neurotoxicity can protect human neurons in vitro from PAF and Abeta, and that targeting secondary apoptotic pathways elicited by PAF can reduce neuronal death in vivo in mouse models of human disease. The identification of compounds capable of inhibiting the primary and secondary PAFR-independent apoptotic events triggered by PAF represents a new means of targeting phospholipid signalling in neurodegenerative disease.

Role of Proteases in the Pathophysiology of Neurodegenerative Diseases

Role of Proteases in the Pathophysiology of Neurodegenerative Diseases Book
Author : Abel Lajtha,Naren L. Banik
Publisher : Springer Science & Business Media
Release : 2007-05-08
ISBN : 0306468476
Language : En, Es, Fr & De

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Book Description :

Researchers seeking problems that offer more hope of success often avoid subjects that seem to be difficult to approach experimentally, or subjects for which experimental results are difficult to interpret. The breakdown part of protein turnover in vivo, particularly in nervous tissue, was such a subject in the past – it was difficult to measure and difficult to explore the mechanisms involved. For factors that influence protein metabolism, it was thought that protein content, function, and distribution are controlled only by the synthetic mechanisms that can supply the needed specificity and response to stimuli. The role of breakdown was thought to be only a general metabolic digestion, elimination of excess polypeptides. We now know that the role of breakdown is much more complex: it has multiple functions, it is coupled to turnover, and it can affect protein composition, function, and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions: it serves to activate and inactivate enzymes, modulate membrane function, alter receptor channel properties, affect transcription and cell cycle, form active peptides, and much more. The hydrolysis of peptide bonds often involves multiple steps, many enzymes, and cycles (such as ubiquination), and often requires the activity of enzyme complexes. Their activation, modification, and inactivation can thus play an important role in biological functions, with numerous families of proteases participating. The specific role of each remains to be elucidated.

Neurodegenerative Diseases

Neurodegenerative Diseases Book
Author : Uday Kishore
Publisher : BoD – Books on Demand
Release : 2013-05-15
ISBN : 9535110888
Language : En, Es, Fr & De

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Book Description :

This book highlights the pathophysiological complexities of the mechanisms and factors that are likely to be involved in a range of neuroinflammatory and neurodegenerative diseases including Alzheimer's disease, other Dementia, Parkinson Diseases and Multiple Sclerosis. The spectrum of diverse factors involved in neurodegeneration, such as protein aggregation, oxidative stress, caspases and secretase, regulators, cholesterol, zinc, microglia, astrocytes, oligodendrocytes, etc, have been discussed in the context of disease progression. In addition, novel approaches to therapeutic interventions have also been presented. It is hoped that students, scientists and clinicians shall find this very informative book immensely useful and thought-provoking.

Pathogenesis of Neurodegenerative Disorders

Pathogenesis of Neurodegenerative Disorders Book
Author : Mark P. Mattson
Publisher : Springer Science & Business Media
Release : 2001-06-01
ISBN : 159259106X
Language : En, Es, Fr & De

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Book Description :

As the average life expectancy of many populations throughout the world increases, so to does the incidence of such age-related neurodegenerative disorders as Alzheimer's, Parkinson's, and Huntington's diseases. Rapid advances in our understanding of the molecular genetics and environmental factors that either cause or increase risk for age-related neurodegenerative disor ders have been made in the past decade. The ability to evaluate, at the cellular and molecular level, abnormalities in postmortem brain tissue from patients, when taken together with the development of valuable animal and cell-culture models of neurodegenerative disorders has allowed the identification of sequences of events within neurons that result in their demise in specific neurodegenerative disorders. Though the genetic and environmental factors that pro mote neurodegeneration may differ among disorders, shared biochemical cascades that will ultimately lead to the death of neurons have been identified. These cascades involve oxyradical production, aberrant regulation of cellular ion homeostasis and activation of a stereotyped sequence of events involving mitochondrial dysfunction and activa tion of specific proteases. Pathogenesis of Neurodegenerative Disorders provides a timely compilation of articles that encompasses fundamental mechanisms involved in neurodegenerative disorders. In addition, mechanisms that may prevent age-related neurodegenerative disorders are presented. Each chapter is written by an expert in the particular neurodegenerative disorder or mechanism or neuronal death discussed.

Neuroinflammation

Neuroinflammation Book
Author : Paul L. Wood
Publisher : Springer Science & Business Media
Release : 2002-12-18
ISBN : 159259297X
Language : En, Es, Fr & De

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Book Description :

In this thoroughly updated and revised edition of his much praised book, Paul L. Wood and a panel of leading researchers capture these new developments in a masterful synthesis of what is known today about the inflammatory mediators and cells involved in neurodegenerative diseases. This second edition contains extensive updates on the mediators produced by microglia and their role in neuroinflammatory-induced neuronal lysis. There is also increased coverage of the animal models used in the study of neuroinflammatory mechanisms, of the new imaging methods that allow the noninvasive evaluation of microglial activation in human neurodegernerative disorders, and of the role of neuroinflammation in amyloid-dependent neuronal lysis.

Advances in Research on Neurodegeneration

Advances in Research on Neurodegeneration Book
Author : Y. Mizuno,D.B. Calne,R. Horowski,W. Poewe,P. Riederer,M.B.H. Youdim
Publisher : Springer Science & Business Media
Release : 2012-12-06
ISBN : 370916284X
Language : En, Es, Fr & De

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Book Description :

We organized the Seventh International Winter Conference on Neurodegeneration and Neuroinflammation in a small town of Karuizawa in Nagano Prefecture in Japan on January 20 to 22, 1999. Karuizawa is a nice summer as well as winter resort close to the place for winter Olympic game in the year of 1998. Over 40 scientists gathered together and made hot discussion. Neurodegeneration and neuroinflammation are two major and important neurologic disorders, in which satisfactory neuroprotective and neurorestorative treatment is not available yet. For this purpose, understanding of molecular mechanisms of neuronal cell death in these two disorders is imperative. Recently, pathologic processes common to these two groups of disorders have been identified such as the involvement of inflammatory changes, microglia, cytokines, and apoptosis. We intended to involve scientists working in these two major fields together to participate in hot and fruitful discussion for the understanding of neuronal death and for developing newer methods of treatment. The science is progressing so rapidly today and we are working in a very narrow specialized area. Sometimes, we are ignorant about important discoveries in other fields. This conference was a nice opportunity for scien tists working different areas to meet together and to exchange their experi ence. This volume is the proceedings of this Winter Conference.

Caspase 3

Caspase 3 Book
Author : Lunawati L. Bennett
Publisher : Nova Science Publishers
Release : 2020-10-30
ISBN : 9781536186109
Language : En, Es, Fr & De

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Book Description :

"Caspase 3: Structure, Functions and Interactions" is a book designed as an educational resource for researchers and health care providers who want to learn more about caspase 3. Physicians, pharmacists, other health care professionals can benefit from learning about the function of caspase 3 and its role in diseases and possible treatment options of using caspase 3-like compounds. New or seasoned scientists with research interests in caspases can learn novel ideas or interventions using caspase 3. Caspases are a family of enzymes that play an important role in developing normal organ formation and function, maintaining homeostasis, and regulating cell death and inflammation. There are 14 known caspase enzymes in mammals, and 12 present in humans. Each caspase varies in purpose and mechanism of action. Caspase-3 is a key cysteine-aspartic protease that is largely known for its role in executing cell death or apoptosis. There are a total of 8 chapters in the book. Chapter 1 introduces the caspase family, their classification, regulation, and role in apoptosis. Chapter 2 discusses caspase-3 role in causing or preventing diseases such as cardiac, diabetes, and cancer. Chapter 3 highlights the emerging roles of caspase-3 in biological processes beyond cell death. Complex regulatory mechanisms are required to coordinate timely and specific activation of caspase 3. As cancer continues to escalate as a major public health concern, caspase 3 role as the prominent executioner of apoptosis plays a central role as a key cellular protein as discussed in Chapter 4. Chapter 5 highlights our understanding on the activation of caspase 3/9 in starfish unfertilized eggs which elucidate the relationship of apoptosis in the vertebrates and nematodes. Chapter 6 discusses the interaction of caspase 3 with apoptotic peptide known as (KLAKLAK)2. Because of the cationic and amphipathic nature of (KLAKLAK)2, this peptide has the unique ability to cause the formation of apoptosome. Chapter 7 identifies caspase 3 role in central nervous system, aging, regeneration of neurons, and in Alzheimer's, Parkinson's, and other neurodegenerative diseases. Chapter 8 discusses biomarker and methods to detect caspase 3, and its interaction with different substrates and compounds. Recent reputable books, journals, monograms, clinical trial results, and hands-on research data are used. This book was written by doctor of philosophy (PhDs) that are doing research in the field of caspase 3. We hope this book become a valuable resource for researchers and others who want to know more about caspase 3 structure, functions and interactions.

Adenoviral Vector mediated Gene Delivery of Dominant negative Caspase 9 Casp9DN Prevents 6 hydroxydopamine 6 OHDA induced Death of Dopaminergic Neurons in Cell Culture But Not in an Adult Rat Model of Parkinson s Disease

Adenoviral Vector mediated Gene Delivery of Dominant negative Caspase 9  Casp9DN  Prevents 6 hydroxydopamine  6 OHDA  induced Death of Dopaminergic Neurons in Cell Culture  But Not in an Adult Rat Model of Parkinson s Disease Book
Author : Allison Denise Ebert
Publisher : Unknown
Release : 2005
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Parkinson's disease (PD) is a neurodegenerative disorder induced by the selective loss of neurons in the brain stem producing the neurotransmitter dopamine (DA). One role for DA is to modulate motor capabilities, and PD is clinically diagnosed by the appearance of various motor disturbances. To date, the cause of sporadic PD is largely unknown. Intense research is underway utilizing PD models to study disease progression and neuronal loss with the goal of developing therapies that halt DA neuron loss, rejuvenate the surviving neurons, and/or replace lost neurons. A better understanding of the molecules involved in DA neuronal loss in PD is needed before therapeutic goals can be achieved. Currently, there is much debate as to whether DA neurons die through a process called apoptosis and if key apoptotic molecules termed caspases are involved. In this thesis I asked two main questions: are apoptotic molecules activated in dopaminergic neurons exposed to a neurotoxin commonly used to create rodent models of PD, and will gene therapy techniques delivering a novel apoptotic inhibitor called dominant-negative caspase-9 (Casp9DN) prevent neuronal death? To address each question, I used the MN9D dopaminergic cell line and adult rats treated with the dopaminergic toxin 6-hydroxydopamine (6-OHDA) to induce selective DA neuron death. My results show that 6-OHDA induces markers of apoptosis and activated caspases in MN9D cells. More importantly, gene delivery of Casp9DN prevents neuronal death in this in vitro model. Data gathered using the 6-OHDA progressive degeneration model in adult rats are remarkably different in that critical caspases are not activated in DA neurons after an intrastriatal injection of 6-OHDA. Strikingly, Casp9DN gene delivery has no effect on DA neuron survival in this in vivo model. Although it is not known how accurately this 6-OHDA model represents human PD, my results support the notion that caspase-independent processes may be involved in the death of DA neurons. Therefore, a treatment strategy for human PD specifically targeting the neuronal death mechanism is likely to require more than inhibition of the apoptotic pathway exclusively at the level of caspase-9.

Proteases in the Brain

Proteases in the Brain Book
Author : Uwe Lendeckel,Nigel M Hooper
Publisher : Springer Science & Business Media
Release : 2006-01-20
ISBN : 0387231013
Language : En, Es, Fr & De

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Book Description :

In all organs of the body, proteases have critical roles to play both in normal development and functioning and in disease states. The brain is no exception to this, with proteases having emerging roles in synaptic plasticity, memory, neurodegenerative disorders such as Alzheimer’s, Parkinson’s and prion diseases, ischemia and traumatic brain injury, inflammatory and infectious diseases, and tumor progression. Proteases in the Brain brings together a wide range of topics under this central theme and highlights the large number of proteases involved in these normal and disease processes. Proteases in the Brain reviews the role and regulation of proteases in, Alzheimer’s disease, brain ischemia and traumatic brain injury, human glioma, inflammatory and infectious diseases of the central nervous system, metabolism of the prion protein, modulating synaptic activity, multiple sclerosis, neuronal plasticity and memory consolidation, Parkinson’s disease, processing, conversion and inactivation of neuropeptides. Proteases in the Brain is a timely and useful source of information both for those well-versed in the role of proteases in the brain, and for those who are beginning to realize the important role of this family of enzymes in brain function and dysfunction.

Selection of Aptamers for CED 9 Bcl 2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer

Selection of Aptamers for CED 9 Bcl 2 Family Cell Death Regulations and Their Application in Study of Apoptosis Regulation and Drug Design for Breast Cancer Book
Author : Anonim
Publisher : Unknown
Release : 2005
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Apoptosis has been found to be conserved from C. elegans to humans, suggesting that novel means developed in C. elegans to modulate apoptosis may also be applied to humans for therapeutic treatments of diseases caused by abnormal apoptosis (e.g. cancer, autoimmune diseases, neurodegenerative diseases, etc). In this study, we employed the technique of SELEX to identify small RNA aptamers with high binding specificity and affinity for key cell death regulators, including CED-9 and CED-4 from C. elegans and Bcl-2 and Bcl-xL from humans. So far, we have isolated five RNA aptamers that bind CED-9 with Kds ranging from 5 nM to 10 nM. These aptamers can be categorized into three groups based on their secondary structures and appear to bind to overlapping sites on CED-9. Furthermore, these CED-9 aptamers can form a ternary complex with CED-9 and EGL-1, but not with CED-9 and CED-4, suggesting that these aptamers and EGL-l bind to different surface regions on CED-9. When over expressed in C. elegans touch receptor neurons, these aptamers can induce ectopic neuronal apoptosis. Importantly, the ectopical cell killing induced by the aptamers is inhibited by a loss-of-function mutation in a key cell-killing gene (ced-3) encoding the caspase, suggesting that these aptamers kill cells through the normal apoptotic pathway. We have conducted several rounds of SELEX experiments on CED-4 and Bcl-xL and obtained candidate molecules with increasing binding affinity in vitro to these two proteins. Our studies suggest that RNA aptamers can be used to modulate apoptosis in vivo and can potentially be used to develop drugs to treat cancers caused by abnormal apoptosis, including breast cancers.

Molecular Mechanisms of Neurodegenerative Diseases

Molecular Mechanisms of Neurodegenerative Diseases Book
Author : Marie-Francoise Chesselet
Publisher : Springer Science & Business Media
Release : 2000-10-19
ISBN : 1592590063
Language : En, Es, Fr & De

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Book Description :

With the unprecedented identification of new mutation mechanisms in neurodegenerative diseases and the emergence of common mechanisms among diseases that were once considered unrelated, neurobiologists are poised for the development of new therapies based on high throughput screenings and a better understanding of the molecular and cellular mechanisms leading to neurodegeneration. In Molecular Mechanisms of Neurodegenerative Diseases, Marie-Francoise Chesselet, MD, PhD, and a panel of leading researchers and neurologists from industry and academia critically review the most recent advances from different yet complementary points of view. Focusing on Alzheimer's, Parkinson's, and CAG triplet repeat diseases, the authors show how studies of cellular and genetically engineered animal models have enhanced our understanding of the molecular mechanisms of neurodegenerative diseases and may lead to the development of new therapeutics. Topics include the role of Ab toxicity, glial cells, and inflammation in Alzheimer's disease; the formation of abnormal protein fragments across several diseases, the impact of dopamine and mitochondrial dysfunction on neurodegeneration; and the potential of genetics to identify the molecular mechanisms of neurodegenerative diseases. Authoritative and insightful, Molecular Mechanisms of Neurodegenerative Diseases synthesizes the novel ideas and concepts now emerging to create a fresh understanding of neurodegenerative disorders, one that promises to lead to powerful new therapies that prevent, delay the onset, slow the progression, or even cure these cruel diseases.

Advanced Understanding of Neurodegenerative Diseases

Advanced Understanding of Neurodegenerative Diseases Book
Author : Raymond Chuen-Chung Chang
Publisher : BoD – Books on Demand
Release : 2011-12-16
ISBN : 9533075295
Language : En, Es, Fr & De

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Book Description :

Advanced Understanding of Neurodegenerative Diseases focuses on different types of diseases, including Alzheimer's disease, frontotemporal dementia, different tauopathies, Parkinson's disease, prion disease, motor neuron diseases such as multiple sclerosis and spinal muscular atrophy. This book provides a clear explanation of different neurodegenerative diseases with new concepts of understand the etiology, pathological mechanisms, drug screening methodology and new therapeutic interventions. Other chapters discuss how hormones and health food supplements affect disease progression of neurodegenerative diseases. From a more technical point of view, some chapters deal with the aggregation of prion proteins in prion diseases. An additional chapter to discuss application of stem cells. This book is suitable for different readers: college students can use it as a textbook; researchers in academic institutions and pharmaceutical companies can take it as updated research information; health care professionals can take it as a reference book, even patients' families, relatives and friends can take it as a good basis to understand neurodegenerative diseases.

Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases

Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases Book
Author : Akhlaq A. Farooqui
Publisher : Springer Science & Business Media
Release : 2010-09-02
ISBN : 1441966528
Language : En, Es, Fr & De

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Book Description :

Collectively, neurodegenerative diseases are characterized by chronic and progressive loss of neurons in discrete areas of the brain, producing debilitating symptoms such as dementia, loss of memory, loss of sensory or motor capability, decreased overall quality of life eventually leading to premature death. Two types of cell death are known to occur during neurodegeneration: (a) apoptosis and (b) necrosis. The necrosis is characterized by the passive cell swelling, intense mitochondrial damage with rapid loss of ATP, alterations in neural membrane permeability, high calcium influx, and disruption of ion homeostasis. This type of cell death leads to membrane lysis and release of intracellular components that induce inflammatory reactions. Necrotic cell death normally occurs at the core of injury site. In contrast, apoptosis is an active process in which caspases (a group of endoproteases with specificity for aspartate residues in protein) are stimulated. Apoptotic cell death is accompanied by cell shrinkage, dynamic membrane blebbing, chromatin condensation, DNA laddering, loss of phospholipids asymmetry, low ATP levels, and mild calcium overload. This type of cell death normally occurs in penumbral region at the ischemic injury site and in different regions in various neurodegenerative diseases.

Mechanism of Reversal of Alzheimer s Disease A beta Induced Neuronal Degeneration in Cultured Human SHSY Cells Using a Neurotrophic Ependymin Mimetic

Mechanism of Reversal of Alzheimer s Disease A beta Induced Neuronal Degeneration in Cultured Human SHSY Cells Using a Neurotrophic Ependymin Mimetic Book
Author : Anonim
Publisher : Unknown
Release : 2007
ISBN : 0987650XXX
Language : En, Es, Fr & De

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Book Description :

Abstract: Alzheimer's disease (AD) is a neurodegenerative disorder that leads to dementia in adults. The mechanism of neurodegeneration is thought to involve the extracellular production of a highly toxic A-beta peptide that engages cell surface receptors to induce cellular oxidative stress and apoptosis, but the signal transduction pathways that lead to A-beta induced cell death are unknown. We previously showed that a human ependymin neurotrophic peptide mimetic (hEPN-1) can promote cell survival in an in vitro AD model system. This initial observation was extended in this thesis by investigating the mechanism of A-beta induced apoptosis and hEPN-1 induced survival. Immunoblots were used to assay the total cellular levels of specific caspase proteins. The results show that A-beta induced apoptosis uses an extrinsic caspase pathway involving caspases-2 and -3, and that hEPN-1 treatment can reduce those caspase levels. A caspase activity assay showed that A-beta increased caspase-3/7 activity, while hEPN-1 treatment lowered it. Moreover, in vivo studies with AD transgenic mice showed that hEPN-1 treatment increased antioxidative superoxide dismutase levels in brain. Thus, hEPN-1 holds potential as a therapeutic to treat the underlying neurodegenerative cause of AD, not merely its symptoms as with other currently approved AD drugs.

Metal based Neurodegeneration

Metal based Neurodegeneration Book
Author : Robert Crichton,Roberta Ward
Publisher : John Wiley & Sons
Release : 2006-05-01
ISBN : 0470022566
Language : En, Es, Fr & De

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Book Description :

This exciting new book opens a window into the causes of debilitating neurological disorders such as Parkinson’s disease, CJD and Huntington’s disease, and gives indications of the prospects for therapy, based on the understanding of molecular defects involved in these diseases. Looking at each specific neurological disorder in turn, the book outlines the role of metals in human biology, in particular in the brain and explores tools for testing potential therapeutic strategies. It concludes with an overview of the potential of both chelation and antioxidant therapy and outlines some perspectives for the future.

Neurodegenerative Diseases

Neurodegenerative Diseases Book
Author : Raymond Chuen-Chung Chang
Publisher : BoD – Books on Demand
Release : 2011-12-09
ISBN : 953307485X
Language : En, Es, Fr & De

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Book Description :

Neurodegenerative Diseases - Processes, Prevention, Protection and Monitoring focuses on biological mechanisms, prevention, neuroprotection and even monitoring of disease progression. This book emphasizes the general biological processes of neurodegeneration in different neurodegenerative diseases. Although the primary etiology for different neurodegenerative diseases is different, there is a high level of similarity in the disease processes. The first three sections introduce how toxic proteins, intracellular calcium and oxidative stress affect different biological signaling pathways or molecular machineries to inform neurons to undergo degeneration. A section discusses how neighboring glial cells modulate or promote neurodegeneration. In the next section an evaluation is given of how hormonal and metabolic control modulate disease progression, which is followed by a section exploring some preventive methods using natural products and new pharmacological targets. We also explore how medical devices facilitate patient monitoring. This book is suitable for different readers: college students can use it as a textbook; researchers in academic institutions and pharmaceutical companies can take it as updated research information; health care professionals can take it as a reference book, even patients' families, relatives and friends can take it as a good basis to understand neurodegenerative diseases.

PHARMACOLOGICAL EFFECTS OF MED

PHARMACOLOGICAL EFFECTS OF MED Book
Author : Cho-Tsun Or,柯楚浚
Publisher : Open Dissertation Press
Release : 2017-01-26
ISBN : 9781361005170
Language : En, Es, Fr & De

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Book Description :

This dissertation, "Pharmacological Effects of Medicinal Herbs on Oxidative Stress Related Neurodegenerative Diseases" by Cho-tsun, Or, 柯楚浚, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Neurodegenerative diseases are characterized by progressive loss and altered functions of neurons. They include Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD). Although there are approved drugs to treat neurodegenerative diseases, most of them only provide symptomatic improvement and have little or no impact on disease progression. Recent findings show that oxidative stress plays an important role in the pathogenesis of neurodegenerative diseases. It could cause apoptosis of neurons. Therefore, rescuing neuronal cell death from oxidative stress challenges could be one of the important therapeutic strategies. Moreover, neural regeneration by neural stem cells is believed to be a potential method for functional recovery after neural damage. The first essential step of neural stem cell therapy is to allow the neural stem cells to survive and grow. Therefore, another aspect of treating neurodegenerative diseases is to search for agents which enhance proliferation of neural stem cells. Herbal medicine is increasingly being used in recent decades to enhance general health and well-being. In this project, three medicinal herbs including Ligusticum chuanxiong (LCX), Ganoderma lucidum (LCZ) and Cimicifuga racemosa (BC) were studied. In the first part of the study, the neuroprotective effects of the three medicinal herbs were tested. Among them, BC and LCX extracts were found to rescue PC12 cells from neuronal cell death induced by hydrogen peroxide (H2O2), as measured by MTT assays. Cim A and Z-lig, bioactive compounds of BC and LCX, respectively, also exerted the neuroprotective effects on PC12 and neuro-2a cells. Both compounds rescued the neuronal cell death via inhibition of apoptosis as measured by caspase-3 activity assays. As for the mechanisms involved, Cim A and Z-lig were found to increase H2O2-suppressed bcl-2 protein expression. Furthermore, Cim A and Z-lig suppressed the phosphorylation of p-38 but had no effect on phosphorylations of JNK, ERK and Akt in H2O2-stimulated neuronal cells. In the second part of the study, the effects of three medicinal herbs on proliferation of human H9-derived neural stem cells were tested. Only LCZ extracts could promote the proliferation of neural stem cells, as measured by MTT assays. It was further shown that LCZ extract enhanced the recovery after oxidative stress damage by H2O2 and nitric oxide. By a series of chemical separations, including solvent partition, column chromatography, and high performance liquid chromatography, a bioactive compound was isolated. It enhanced the proliferation of neural stem cells as measured by MTT and BrdU assays. The underlying mechanisms were investigated. It was found that Compound LCZ could induce the mRNA levels of CYP1B1 and HDAC9. However, these proteins did not play a role in enhanced proliferation of neural stem cells induced by Compound LCZ. Additionally, compound LCZ increased the phosphorylation of ERK but had no effect on phosphorylations of JNK, Akt and PI3K kinases. This activation of ERK correlated with the promotion of proliferation, as confirmed by an MEK inhibitor. Taken together, the study reveals that medicinal herbs LCX, BC and LCZ are potential drug candidates for treating oxidative stress related neurodegenerative diseases. Subjects: Materia medica Nervous system - Degeneration - T

Neuro inflammation in Neuronal Death and Repair

Neuro inflammation in Neuronal Death and Repair Book
Author : Anonim
Publisher : Elsevier
Release : 2007-07-25
ISBN : 0080550568
Language : En, Es, Fr & De

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Book Description :

Neuroinflammation has been implicated recently in the pathogenesis of many neurodegenerative diseases. The cross-talk between neurons and non-neuronal cells seems to be a critical step in the progression of neurodegeneration and molecules that have a beneficial role may turn into harmful players. Thus, matrix metalloproteinases (MMPs), which are involved in axonal growth and regeneration as well as synaptic plasticity, may also have detrimental effects. Recent evidence has linked MMPs to conditions like ischemia, multiple sclerosis, Alzheimer's disease and suggested that, together with their role in the degradation of extracellular macromolecules, MMPs could work as important signalling molecules from injured neurons to the microglia. Thus, MMP-3 has been shown to induce the release of pro-inflammatory cytokines from microglia via activation of ERK and NF-kB-dependent pathways. Increasing evidence highlights the importance of a balanced cross-talk between neurons and non-neuronal cells and indicates that the presence of reactive astrocytes, the activation of microglia and the release of inflammatory mediators may contribute to the progression of many central nervous system disorders, independently of the nature of the primary pathogenic event. However, many aspects still remain controversial and much more effort is needed to understand the role of neuroinflammatory mediators and processes in these conditions. This volume brings together renowned, international scientists to discuss current knowledge and views on the mechanisms of neuroinflammation, on its role in the context of different neurodegenerative diseases (i.e. Alzheimer's, prion disease, HIV-associated dementia, multiple sclerosis, pain) and on the potential approaches for future therapeutic strategies.

Milestones in Neurotoxicity and Neuroprotection A Tribute to Professor Toshiharu Nagatsu

Milestones in Neurotoxicity and Neuroprotection  A Tribute to Professor Toshiharu Nagatsu Book
Author : M. Naoi,W. Maruyama,M.A. Collins,S. Hasan Parvez,M B H Youdim
Publisher : Gulf Professional Publishing
Release : 2002-10-09
ISBN : 9780444510365
Language : En, Es, Fr & De

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Book Description :

This book summarizes recent advances in understanding the mechanism underlying the selective cell death of dopamine neurons in Parkinson's disease. MPTP, endogenous neurotoxins, L-DOPA, and metal were proved to induce apoptosis and necrosis in neurons. The relationship of these causal factors to the pathogenesis of Parkinson's disease was discussed to give us overviews on the role of neurotoxins in this degenerative disorder. This title further presents the intracellular signal transduction, and the related enzymes and other factors involved in dopaminergic neuronal death. Recent results on intracellular mechanism of neuroprotection are presented, suggesting that neuroprotection as a causal therapy of neurodegenerative disorders may become practical in near future. This book shows new neuroprotective agents, such as propargylamine derivatives and neurotrophins, and the intracellular mechanism to prevent the activation of apoptotic cascade in neurons. The authors of this book are active researchers participating in these subjects and the readers will find the knowledge and techniques for the study on neurotoxicity and neuroprotection, and the strategy for future research on these important subjects in clinical and basic neurology and neurosciences. The book is dedicated to Professor Toshiharu Nagatsu, a pioneer in the search for pathogenic factors in Parkinson's disease. The book is reprinted from the journal 'Neurotoxicology and Teratology', Volume 24/5.