Author: Grzegorz Kreiner
Publisher: Frontiers Media SA
ISBN: 2889715639
Category : Science
Languages : en
Pages : 280
Book Description
Common Pathways Linking Neurodegenerative Diseases – The Role of Inflammation
Author: Grzegorz Kreiner
Publisher: Frontiers Media SA
ISBN: 2889715639
Category : Science
Languages : en
Pages : 280
Book Description
Publisher: Frontiers Media SA
ISBN: 2889715639
Category : Science
Languages : en
Pages : 280
Book Description
Clinical Immunology
Author: Robert R. Rich
Publisher: Mosby Incorporated
ISBN: 9780323044042
Category : Medical
Languages : en
Pages : 1578
Book Description
Offers answers to challenges in clinical immunology. This book contains immunology knowledge and includes a companion web site to give you two ways to find the answers you need.
Publisher: Mosby Incorporated
ISBN: 9780323044042
Category : Medical
Languages : en
Pages : 1578
Book Description
Offers answers to challenges in clinical immunology. This book contains immunology knowledge and includes a companion web site to give you two ways to find the answers you need.
The Molecular and Cellular Basis of Neurodegenerative Diseases
Author: Michael S. Wolfe
Publisher: Academic Press
ISBN: 0128113057
Category : Medical
Languages : en
Pages : 561
Book Description
The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer's, Parkinson's, frontotemporal dementia, ALS, Huntington's, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. - Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features - Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration - Details features, advantages and limitations of animal models, as well as prospects for therapeutic development - Authored by internationally recognized leaders in the field - Includes illustrations that help clarify and consolidate complex concepts
Publisher: Academic Press
ISBN: 0128113057
Category : Medical
Languages : en
Pages : 561
Book Description
The Molecular and Cellular Basis of Neurodegenerative Diseases: Underlying Mechanisms presents the pathology, genetics, biochemistry and cell biology of the major human neurodegenerative diseases, including Alzheimer's, Parkinson's, frontotemporal dementia, ALS, Huntington's, and prion diseases. Edited and authored by internationally recognized leaders in the field, the book's chapters explore their pathogenic commonalities and differences, also including discussions of animal models and prospects for therapeutics. Diseases are presented first, with common mechanisms later. Individual chapters discuss each major neurodegenerative disease, integrating this information to offer multiple molecular and cellular mechanisms that diseases may have in common. This book provides readers with a timely update on this rapidly advancing area of investigation, presenting an invaluable resource for researchers in the field. - Covers the spectrum of neurodegenerative diseases and their complex genetic, pathological, biochemical and cellular features - Focuses on leading hypotheses regarding the biochemical and cellular dysfunctions that cause neurodegeneration - Details features, advantages and limitations of animal models, as well as prospects for therapeutic development - Authored by internationally recognized leaders in the field - Includes illustrations that help clarify and consolidate complex concepts
Apolipoprotein E and Alzheimer’s Disease
Author: A.D. Roses
Publisher: Springer Science & Business Media
ISBN: 3642801099
Category : Medical
Languages : en
Pages : 208
Book Description
There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.
Publisher: Springer Science & Business Media
ISBN: 3642801099
Category : Medical
Languages : en
Pages : 208
Book Description
There is now considerable genetic evidence that the type 4 allele of the apolipoprotein E gene is a major susceptibility factor associated with late-onset Alzheimer's disease, the common form of the disease defined as starting after sixty years of age. The role of apolipoprotein E in normal brain metabolism and in the pathogenesis of Alzheimer's disease are new and exciting avenues of research. This book, written by the most outstanding scientists in this new filed, is the first presentation of results concerning the implications of apolipoprotein E on the genetics, cell biology, neuropathology, biochemistry, and therapeutic management of Alzheimer's disease.
The Propagation of Neurodegenerative Diseases by Inflammation and Exosomes
Author: Valerie Sackmann
Publisher: Linköping University Electronic Press
ISBN: 9175190125
Category :
Languages : en
Pages : 69
Book Description
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases with rates increasing along with the ageing global population. Despite best efforts, we still do not understand the etiopathogenesis of these diseases and there are no effective disease-modifying treatments. Cognitive deficiencies or motor complications that emerge during AD and PD are thought to be the result of the accumulation of misfolded, aggregate-prone proteins, such as amyloid-? (A?) and tau or ?-synuclein (?-syn), respectively. Growing evidence suggests that prefibrillar oligomers of A? and ?-syn (oA? and o?-syn) are key contributors to the progression of these diseases. The progressive accumulation of these proteins leads to a gradual spread of pathology throughout interconnected brain regions, but the mechanisms by which this spreading occurs are still largely unknown. Neuroinflammation has been recognised as an important contributor to neurodegenerative disease. It is hypothesised that a pro-inflammatory environment initiated by the innate immune system, either through activation from A? itself or indirectly through neuronal injury signals in AD. These phenomena are thought to either cause or accelerate AD, such that an anti-inflammatory approach may be neuroprotective. In paper I, we investigated whether different inflammatory environments affected the transfer of oA? between neuron-like cells, in addition to investigating inter- and intracellular protein changes. This study demonstrated that an anti-inflammatory environment reduces the transfer of oA? between cells. We also provide evidence that these cells begin to take on the “phenotype” of the inflammatory milieu, while also demonstrating that the expression profile of endosomal/lysosomal and protein trafficking proteins is altered during these conditions. Small extracellular vesicles called exosomes, which are key players in cell to cell communication, have been proposed to play an influential role in spreading neurodegenerative proteins between cells. Exosomes are small membranous vesicles that are formed by the inward budding of multivesicular bodies (MVBs). These MVBs can then merge with the plasma membrane to be released into the extracellular environment as vesicles, which serve as vehicles for transferring proteins, lipids, and mRNAs between cells. The ESCRT-dependent pathway is the most understood mechanism underlying exosome biogenesis. However, exosomes can also be formed through ESCRT-independent pathways, including through the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2), which produces ceramide. Paper II investigated whether exosomes formed through an ESCRT-independent pathway plays a significant role in the transfer of o?-syn between neuron-like cells. As oxidative stress is a common feature in PD brains, which in turn dysregulates nSMase2 activity, we also tested our model under hypoxic conditions. Inhibition of nSMase2 significantly reduced the transfer of o?-syn between cells but also resulted in decreased ?-syn aggregation. Hypoxia did not influence o?-syn transfer, however, it significantly dysregulated the sphingolipid composition, which may be important for ?-syn binding to exosomes and exosome communication. During AD and PD, there is a noted reduction in the effectiveness of autophagy, a process critical to cellular proteostasis. Recent studies have uncovered shared regulatory mechanisms of exosome biogenesis and autophagy, suggesting that they are closely linked. Previous findings have shown that inhibition of autophagy in AD mice mediates A? trafficking through altering the secretion of A? in MVBs. To further study this effect, we investigated the interplay between autophagy and exosome secretion using ATG7 knock-out x APPNL-F knock-in AD mice in paper III. These autophagy-deficient AD mice had a reduced extracellular A? plaque load, but increased intracellular A?, which was found to be assembled into higher-ordered assemblies. While exosomal secretion was dysregulated in these mice, the amount of A? packaged into the exosomes was unchanged. Lastly, one of the biggest challenges in developing effective treatments for AD is the lack of early diagnosis of living patients. As the connection between exosomes and the spread of neurodegenerative proteins is still relatively new, there remains a diagnostic potential to be explored with exosomes. Paper IV aimed to develop a new diagnostic assay to detect oA? in exosomes isolated from human cerebrospinal fluid. Although exosomal oA? was readily detected in some of these samples, the assay’s sensitivity requires additional optimisation before it can be further validated for the clinic. In summary, the studies presented in this thesis have furthered our understanding of how inflammation, autophagy, and exosomes contribute to the intercellular transmission of AD and PD associated proteins. We have shown that an anti-inflammatory approach may slow down the progression of AD through reducing the transfer of oA? between cells. We also provide novel findings relating to the biogenesis of exosomes, which in turn affected the ability of exosomes to transmit neurodegenerative proteins between cells, and their association with autophagic processes. Finally, we have investigated the feasibility of exosomes as an early AD diagnostic marker. This work has helped to elucidate some of the mechanisms underlying the progression of neurodegenerative diseases, which may be useful targets for the investigation of new therapeutic avenues.
Publisher: Linköping University Electronic Press
ISBN: 9175190125
Category :
Languages : en
Pages : 69
Book Description
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases with rates increasing along with the ageing global population. Despite best efforts, we still do not understand the etiopathogenesis of these diseases and there are no effective disease-modifying treatments. Cognitive deficiencies or motor complications that emerge during AD and PD are thought to be the result of the accumulation of misfolded, aggregate-prone proteins, such as amyloid-? (A?) and tau or ?-synuclein (?-syn), respectively. Growing evidence suggests that prefibrillar oligomers of A? and ?-syn (oA? and o?-syn) are key contributors to the progression of these diseases. The progressive accumulation of these proteins leads to a gradual spread of pathology throughout interconnected brain regions, but the mechanisms by which this spreading occurs are still largely unknown. Neuroinflammation has been recognised as an important contributor to neurodegenerative disease. It is hypothesised that a pro-inflammatory environment initiated by the innate immune system, either through activation from A? itself or indirectly through neuronal injury signals in AD. These phenomena are thought to either cause or accelerate AD, such that an anti-inflammatory approach may be neuroprotective. In paper I, we investigated whether different inflammatory environments affected the transfer of oA? between neuron-like cells, in addition to investigating inter- and intracellular protein changes. This study demonstrated that an anti-inflammatory environment reduces the transfer of oA? between cells. We also provide evidence that these cells begin to take on the “phenotype” of the inflammatory milieu, while also demonstrating that the expression profile of endosomal/lysosomal and protein trafficking proteins is altered during these conditions. Small extracellular vesicles called exosomes, which are key players in cell to cell communication, have been proposed to play an influential role in spreading neurodegenerative proteins between cells. Exosomes are small membranous vesicles that are formed by the inward budding of multivesicular bodies (MVBs). These MVBs can then merge with the plasma membrane to be released into the extracellular environment as vesicles, which serve as vehicles for transferring proteins, lipids, and mRNAs between cells. The ESCRT-dependent pathway is the most understood mechanism underlying exosome biogenesis. However, exosomes can also be formed through ESCRT-independent pathways, including through the hydrolysis of sphingomyelin by neutral sphingomyelinase 2 (nSMase2), which produces ceramide. Paper II investigated whether exosomes formed through an ESCRT-independent pathway plays a significant role in the transfer of o?-syn between neuron-like cells. As oxidative stress is a common feature in PD brains, which in turn dysregulates nSMase2 activity, we also tested our model under hypoxic conditions. Inhibition of nSMase2 significantly reduced the transfer of o?-syn between cells but also resulted in decreased ?-syn aggregation. Hypoxia did not influence o?-syn transfer, however, it significantly dysregulated the sphingolipid composition, which may be important for ?-syn binding to exosomes and exosome communication. During AD and PD, there is a noted reduction in the effectiveness of autophagy, a process critical to cellular proteostasis. Recent studies have uncovered shared regulatory mechanisms of exosome biogenesis and autophagy, suggesting that they are closely linked. Previous findings have shown that inhibition of autophagy in AD mice mediates A? trafficking through altering the secretion of A? in MVBs. To further study this effect, we investigated the interplay between autophagy and exosome secretion using ATG7 knock-out x APPNL-F knock-in AD mice in paper III. These autophagy-deficient AD mice had a reduced extracellular A? plaque load, but increased intracellular A?, which was found to be assembled into higher-ordered assemblies. While exosomal secretion was dysregulated in these mice, the amount of A? packaged into the exosomes was unchanged. Lastly, one of the biggest challenges in developing effective treatments for AD is the lack of early diagnosis of living patients. As the connection between exosomes and the spread of neurodegenerative proteins is still relatively new, there remains a diagnostic potential to be explored with exosomes. Paper IV aimed to develop a new diagnostic assay to detect oA? in exosomes isolated from human cerebrospinal fluid. Although exosomal oA? was readily detected in some of these samples, the assay’s sensitivity requires additional optimisation before it can be further validated for the clinic. In summary, the studies presented in this thesis have furthered our understanding of how inflammation, autophagy, and exosomes contribute to the intercellular transmission of AD and PD associated proteins. We have shown that an anti-inflammatory approach may slow down the progression of AD through reducing the transfer of oA? between cells. We also provide novel findings relating to the biogenesis of exosomes, which in turn affected the ability of exosomes to transmit neurodegenerative proteins between cells, and their association with autophagic processes. Finally, we have investigated the feasibility of exosomes as an early AD diagnostic marker. This work has helped to elucidate some of the mechanisms underlying the progression of neurodegenerative diseases, which may be useful targets for the investigation of new therapeutic avenues.
Transactions of the Royal Society of South Australia, Incorporated
Author: Royal Society of South Australia
Publisher:
ISBN:
Category : Natural history
Languages : en
Pages : 318
Book Description
Publisher:
ISBN:
Category : Natural history
Languages : en
Pages : 318
Book Description
The Brain Under Siege
Author: Howard L. Weiner
Publisher: BenBella Books
ISBN: 1953295886
Category : Science
Languages : en
Pages : 285
Book Description
1 in 6 people suffer from brain diseases like MS, Parkinson’s, and Alzheimer’s. Now, a Harvard neurologist takes you inside the brain under attack—and illuminates the path to a cure. Multiple Sclerosis. Parkinson’s Disease. Alzheimer’s. ALS. Chances are, you know someone with a neurologic disease. Because the brain controls so much and is integral to our identity, the diseases that affect it are uniquely devastating both to patients and families. And because it remains the most mysterious of our vital organs, treating the brain is an ongoing puzzle. In The Brain Under Siege, Howard Weiner likens the brain to a crime scene, showing readers how “clues” point to causes and suggest paths to a cure. He takes readers on a journey through the latest technological advances, exploring which routes of investigation have gone cold and which have led to breakthroughs. Readers couldn’t ask for a better guide: A professor of neurology at Harvard Medical School and co-director of the Ann Romney Center for Neurologic diseases, Weiner is an internationally renowned expert, who pioneered immunotherapy in MS and is currently investigating an Alzheimer’s vaccine. Informative and engaging, this groundbreaking book tells the story behind the science—painting a picture of the discoveries, setbacks, false leads, and victories on the front lines of brain research. Weiner also offers unique insight by exploring the experiences of the brave patients and families who make cutting-edge clinical trials possible. Both a clear-eyed assessment of where the science stands and a gripping and poignant narrative of the dramatic pursuit for a cure, The Brain Under Siege is a must-read for patients, families, and anyone interested in unraveling the mysteries of the brain.
Publisher: BenBella Books
ISBN: 1953295886
Category : Science
Languages : en
Pages : 285
Book Description
1 in 6 people suffer from brain diseases like MS, Parkinson’s, and Alzheimer’s. Now, a Harvard neurologist takes you inside the brain under attack—and illuminates the path to a cure. Multiple Sclerosis. Parkinson’s Disease. Alzheimer’s. ALS. Chances are, you know someone with a neurologic disease. Because the brain controls so much and is integral to our identity, the diseases that affect it are uniquely devastating both to patients and families. And because it remains the most mysterious of our vital organs, treating the brain is an ongoing puzzle. In The Brain Under Siege, Howard Weiner likens the brain to a crime scene, showing readers how “clues” point to causes and suggest paths to a cure. He takes readers on a journey through the latest technological advances, exploring which routes of investigation have gone cold and which have led to breakthroughs. Readers couldn’t ask for a better guide: A professor of neurology at Harvard Medical School and co-director of the Ann Romney Center for Neurologic diseases, Weiner is an internationally renowned expert, who pioneered immunotherapy in MS and is currently investigating an Alzheimer’s vaccine. Informative and engaging, this groundbreaking book tells the story behind the science—painting a picture of the discoveries, setbacks, false leads, and victories on the front lines of brain research. Weiner also offers unique insight by exploring the experiences of the brave patients and families who make cutting-edge clinical trials possible. Both a clear-eyed assessment of where the science stands and a gripping and poignant narrative of the dramatic pursuit for a cure, The Brain Under Siege is a must-read for patients, families, and anyone interested in unraveling the mysteries of the brain.
Diabetes and the Nervous System
Author: Douglas W. Zochodne
Publisher: Elsevier
ISBN: 9780444534804
Category : Medical
Languages : en
Pages : 0
Book Description
This is a unique compilation, by experts worldwide, addressing how diabetes impacts the nervous system. For example, diabetic polyneuropathy, a disorder more common than MS, Parkinson's disease, and ALS combined, is a major source of disability to diabetic persons worldwide. This book addresses diabetic polyneuropathy and how diabetes alters other parts of the nervous system.
Publisher: Elsevier
ISBN: 9780444534804
Category : Medical
Languages : en
Pages : 0
Book Description
This is a unique compilation, by experts worldwide, addressing how diabetes impacts the nervous system. For example, diabetic polyneuropathy, a disorder more common than MS, Parkinson's disease, and ALS combined, is a major source of disability to diabetic persons worldwide. This book addresses diabetic polyneuropathy and how diabetes alters other parts of the nervous system.
Oxidative Stress and Neurodegenerative Disorders
Author: G. Ali Qureshi
Publisher: Elsevier
ISBN: 0080489494
Category : Science
Languages : en
Pages : 795
Book Description
Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.* Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems
Publisher: Elsevier
ISBN: 0080489494
Category : Science
Languages : en
Pages : 795
Book Description
Oxidative stress is the result of an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. Brain cells are continuously exposed to reactive oxygen species generated by oxidative metabolism, and in certain pathological conditions defense mechanisms against oxygen radicals may be weakened and/or overwhelmed. DNA is a potential target for oxidative damage, and genomic damage can contribute to neuropathogenesis. It is important therefore to identify tools for the quantitative analysis of DNA damage in models on neurological disorders. This book presents detailed information on various neurodegenerative disorders and their connection with oxidative stress. This information will provide clinicians with directions to treat these disorders with appropriate therapy and is also of vital importance for the drug industries for the design of new drugs for treatment of degenerative disorders.* Contains the latest information on the subject of neurodegenerative disorders* Reflects on various factors involved in degeneration and gives suggestions for how to tackle these problems
Etiology of Parkinson's Disease
Author: Jonas H. Ellenberg
Publisher: CRC Press
ISBN: 9780824788230
Category : Medical
Languages : en
Pages : 600
Book Description
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.
Publisher: CRC Press
ISBN: 9780824788230
Category : Medical
Languages : en
Pages : 600
Book Description
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.