The Experts below are selected from a list of 99 Experts worldwide ranked by ideXlab platform
Bosch Pont, Mª Neus - One of the best experts on this subject based on the ideXlab platform.
-
Desenvolupament d’una teràpia anti-amiloide per a la malaltia d’Alzheimer en el gos amb disfunció cognitiva
'Edicions de la Universitat de Barcelona', 2012Co-Authors: Bosch Pont, Mª NeusAbstract:[cat] Introducció: La Malaltia d’Alzheimer (AD), és la malaltia neurodegenerativa amb més incidència actualment. La hipòtesi més acceptada sobre l’origen de la malaltia és la “hipòtesi amiloide”, en la que el cúmul de pèptid beta amiloide (Aβ) a l’espai extracel•lular a cervell du a la formació d’oligòmers solubles, fibril•les i plaques provocant una disfunció sinàptica i neuronal i, conseqüentment, dèficits cognitius. Tots aquests esdeveniments van acompanyats de neuroinflamació i de la formació de cabdells Neurofibril•lars. Diversos són els models animals utilitzats per a l’estudi l’AD, dintre dels quals hi trobem els gossos de companyia envellits s’ha descrit la Síndrome de Disfunció Cognitiva (CDS). Els gossos amb la CDS es caracteritzen per presentar per alteracions a nivell cognitiu, anatòmic i histopatològic similars les descrites anteriorment i comparables a les observades en els estadis inicials de l’AD. Totes aquestes convergències, fan que el gos amb la CDS sigui considerat un bon model natural d’envelliment humà i dels estadis més inicials de l’AD i que pugui ser de gran utilitat en estudis de tractaments dirigits l’AD. Dintre dels tractaments dirigits a la prevenció de la formació i/o eliminació d’amiloide hi trobem les immunoteràpies anti-amiloide actives. Aquestes, mitjançant l’administració d’un fragment d’Aβ sintètic combinat amb diversos adjuvants i proteïnes transportadores, indueix l’eliminació d’amiloide de Sistema Nerviós Central cap a la perifèria mitjançant diversos mecanismes. Des de l’estudi fet l’any 2000 amb la immunoteràpia (AN1792), dissenyada a partir de l’Aβ42 i QS21 com a adjuvant, que va provocar un 6% de casos de meningoencefalitis en els pacients inclosos a l’estudi, diversos han estat els esforços per dissenyar vacunes eficaces i que evitin els efectes secundaris no desitjats. Objectiu general: En aquest treball es planteja si l’administració d’una immunoteràpia dissenyada a partir d’un adjuvant que indueix respostes de tipus Th2 o anti-inflamatòria juntament amb un fragment C-terminal del pèptid Aβ fibril•lar indueix una millora cognitiva en gossos amb CDS, evitant els efectes nocius observats en immunoteràpies ja testades en humans.[eng] Development of an anti-amyloid therapy for Alzheimer Disease in dogs with Cognitive Dysfunction Introduction: Alzheimer’s Disease (AD) is a neurodegenerative disease where the cognitive deficits are due to the accumulation of the different forms of amyloid beta peptide (Aβ) (oligomers, fibrils and plaques). They also induce neuroinflamation and the formation of the Neurofibrillary tangles. Aged dogs with Cognitive Dysfunction Syndrome (CDS) also present cognitive deficits associated to the accumulation of the different forms of Aβ into the brain. Because of the similarities with AD, dogs with CDS are considered a good model for the study of aging human and the first stages of AD. Active anti-amyloid immunotherapy is one of the strategies proposed with the aim to ameliorate the cognitive deficits through the clearance of the amyloid burden from the central nervous system to the periphery. After the harmful side effects due to the administration of the immunotherapy AN1792 in the 21st century, studies with different anti-amyloid immunotherapies have been performed with the aim to prevent and/or ameliorate AD and avoiding the side affects. Objective: This work considers the development of an immunotherapy designed with a Th2 adjuvant and C-terminal fragments of the fibrillar Aβ to induce a cognitive improvement in CDS dogs avoiding the side effects of the immunotherapies tested in humans. Results: The immunization study was performed after the selection of the V5 vaccine designed using the mixture of the Aβ1-40 + KLH-Aβy-40 fragments and the Aluminium Hydroxide (Alum®) as the adjuvant. V5 vaccine was administrated during a fifty days period to CDS dogs (n=12) and housed adult beagle dogs (n=9). Changes in cognitive deficits, in biochemistry and haematologist biomarkers were observed during the follow-up period. With the aim to observe the changes in neuroinflamation responses, a comparative study between brain samples form unimmunized and immunized dogs was performed as well. Increases in the Aβplasma/ AβLCR ratio associated to the reduction of the neuroinflamation responses could diminish the neuronal damage leading to a cognitive improvement without side effects in CDS dogs
-
Desenvolupament d’una teràpia anti-amiloide per a la malaltia d’Alzheimer en el gos amb disfunció cognitiva
'Edicions de la Universitat de Barcelona', 2012Co-Authors: Bosch Pont, Mª NeusAbstract:Introducció: La Malaltia d’Alzheimer (AD), és la malaltia neurodegenerativa amb més incidència actualment. La hipòtesi més acceptada sobre l’origen de la malaltia és la “hipòtesi amiloide”, en la que el cúmul de pèptid beta amiloide (Aβ) a l’espai extracel•lular a cervell du a la formació d’oligòmers solubles, fibril•les i plaques provocant una disfunció sinàptica i neuronal i, conseqüentment, dèficits cognitius. Tots aquests esdeveniments van acompanyats de neuroinflamació i de la formació de cabdells Neurofibril•lars. Diversos són els models animals utilitzats per a l’estudi l’AD, dintre dels quals hi trobem els gossos de companyia envellits s’ha descrit la Síndrome de Disfunció Cognitiva (CDS). Els gossos amb la CDS es caracteritzen per presentar per alteracions a nivell cognitiu, anatòmic i histopatològic similars les descrites anteriorment i comparables a les observades en els estadis inicials de l’AD. Totes aquestes convergències, fan que el gos amb la CDS sigui considerat un bon model natural d’envelliment humà i dels estadis més inicials de l’AD i que pugui ser de gran utilitat en estudis de tractaments dirigits l’AD. Dintre dels tractaments dirigits a la prevenció de la formació i/o eliminació d’amiloide hi trobem les immunoteràpies anti-amiloide actives. Aquestes, mitjançant l’administració d’un fragment d’Aβ sintètic combinat amb diversos adjuvants i proteïnes transportadores, indueix l’eliminació d’amiloide de Sistema Nerviós Central cap a la perifèria mitjançant diversos mecanismes. Des de l’estudi fet l’any 2000 amb la immunoteràpia (AN1792), dissenyada a partir de l’Aβ42 i QS21 com a adjuvant, que va provocar un 6% de casos de meningoencefalitis en els pacients inclosos a l’estudi, diversos han estat els esforços per dissenyar vacunes eficaces i que evitin els efectes secundaris no desitjats. Objectiu general: En aquest treball es planteja si l’administració d’una immunoteràpia dissenyada a partir d’un adjuvant que indueix respostes de tipus Th2 o anti-inflamatòria juntament amb un fragment C-terminal del pèptid Aβ fibril•lar indueix una millora cognitiva en gossos amb CDS, evitant els efectes nocius observats en immunoteràpies ja testades en humans.Development of an anti-amyloid therapy for Alzheimer Disease in dogs with Cognitive Dysfunction Introduction: Alzheimer’s Disease (AD) is a neurodegenerative disease where the cognitive deficits are due to the accumulation of the different forms of amyloid beta peptide (Aβ) (oligomers, fibrils and plaques). They also induce neuroinflamation and the formation of the Neurofibrillary tangles. Aged dogs with Cognitive Dysfunction Syndrome (CDS) also present cognitive deficits associated to the accumulation of the different forms of Aβ into the brain. Because of the similarities with AD, dogs with CDS are considered a good model for the study of aging human and the first stages of AD. Active anti-amyloid immunotherapy is one of the strategies proposed with the aim to ameliorate the cognitive deficits through the clearance of the amyloid burden from the central nervous system to the periphery. After the harmful side effects due to the administration of the immunotherapy AN1792 in the 21st century, studies with different anti-amyloid immunotherapies have been performed with the aim to prevent and/or ameliorate AD and avoiding the side affects. Objective: This work considers the development of an immunotherapy designed with a Th2 adjuvant and C-terminal fragments of the fibrillar Aβ to induce a cognitive improvement in CDS dogs avoiding the side effects of the immunotherapies tested in humans. Results: The immunization study was performed after the selection of the V5 vaccine designed using the mixture of the Aβ1-40 + KLH-Aβy-40 fragments and the Aluminium Hydroxide (Alum®) as the adjuvant. V5 vaccine was administrated during a fifty days period to CDS dogs (n=12) and housed adult beagle dogs (n=9). Changes in cognitive deficits, in biochemistry and haematologist biomarkers were observed during the follow-up period. With the aim to observe the changes in neuroinflamation responses, a comparative study between brain samples form unimmunized and immunized dogs was performed as well. Increases in the Aβplasma/ AβLCR ratio associated to the reduction of the neuroinflamation responses could diminish the neuronal damage leading to a cognitive improvement without side effects in CDS dogs
Xiaomin Wang - One of the best experts on this subject based on the ideXlab platform.
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and b-Amyloid Deposition in Alzheimer’s Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. b-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Ab generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Ab. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Ab generation and also down-regulated the expression of b-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and β-Amyloid Deposition in Alzheimer's Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer's disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. β-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.
Eugenio Frixione - One of the best experts on this subject based on the ideXlab platform.
-
neura nerves nerve fibers Neurofibrils microtubules multidimensional routes of pain pleasure and voluntary action in images across the ages
Progress in Brain Research, 2013Co-Authors: Eugenio FrixioneAbstract:Available records indicate that the human body has always been conceived, in different periods and cultures, as spanned by multiple channels for internal communication and coherent functioning as a unit—“meridians” in treatises of Chinese medicine, metu in Egyptian papyri, srotas in Ayurvedic Indian texts, and neura in the Western scientific heritage from ancient Greece. Unfortunately, the earliest extant figurative depictions of such pathways of general control, complementary to the blood vessels, are late medieval copies of old crude sketches that attempted to show the main anatomico-physiological systems. The scarcity of adequate illustrations was more than compensated in the Renaissance, when the efforts of both artists and anatomists for the first time produced basically correct renditions of the human nervous system and many other bodily structures. As attention was next focused on microscopic structure as a requisite to understand physiological mechanisms, during the Enlightenment the nerves were revealed to consist of numerous thin tubes or fibers aligned in parallel. Improved microscopy techniques in the nineteenth century led to discovering and delineating still finer fibrils coursing along the cores of the nerve fibers themselves. Electron microscopy, developed throughout the twentieth century, recognized some of these fibrils within nerve fibers as being also tubular. All the progressive stages in understanding nerve construction, at increasingly more detailed scales, have been accompanied by technological advances and by debate about the structure and function relationship. And every step has been a source of amazing imagery.
-
cajal s second great battle for the neuron doctrine the nature and function of Neurofibrils
Brain Research Reviews, 2009Co-Authors: Eugenio FrixioneAbstract:Abstract One hundred years ago, a novel kind of reticularism threatened to displace the neuron doctrine as the established model of functional organization of the nervous system. The challenging paradigm, championed by Stephan von Apathy and Albrecht Bethe, held that nerve impulses propagate along Neurofibrils connected in a continuous network throughout all nerve cells. Santiago Ramon y Cajal, a leading figure in the conception of the neuron doctrine, headed again the battle against this return of reticularism. Dissatisfied with the available staining techniques, he devised the “reduced silver nitrate method” that even Camillo Golgi recognized as the best at the time for revealing the Neurofibrils. In 1904 Cajal already published over a dozen papers in three languages describing Neurofibril distributions in the nervous systems of diverse vertebrates and invertebrates, under both normal and experimental conditions. Next he investigated the involvement of Neurofibrils in the process of nerve regeneration. This unprecedented survey led him to the conclusion that the Neurofibrils are linear “colonies” of particles constituting a semi-solid, dynamic internal skeleton of the nerve cell. Apathy reacted with a long invective paper that Cajal had no choice but acknowledging. His comprehensive reply, published in 1908, meant the effective end of the renewed reticularist campaign against the neuron doctrine. Along the way, a visionary and today almost forgotten chapter in the history of the cytoskeleton had also been written.
Yan Zheng - One of the best experts on this subject based on the ideXlab platform.
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and b-Amyloid Deposition in Alzheimer’s Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. b-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Ab generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Ab. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Ab generation and also down-regulated the expression of b-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and β-Amyloid Deposition in Alzheimer's Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer's disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. β-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.
Qi Wang - One of the best experts on this subject based on the ideXlab platform.
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and b-Amyloid Deposition in Alzheimer’s Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. b-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Ab generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Ab. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Ab generation and also down-regulated the expression of b-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD
-
Involvement of Receptor Tyrosine Kinase Tyro3 in Amyloidogenic APP Processing and β-Amyloid Deposition in Alzheimer's Disease Models
2012Co-Authors: Yan Zheng, Qi Wang, Bing Xiao, Yizheng Wang, Xiaomin WangAbstract:Alzheimer's disease (AD) is the most common progressive neurodegenerative disease known to humankind. It is characterized by brain atrophy, extracellular amyloid plaques, and intracellular Neurofibril tangles. β-amyloid cascade is considered the major causative player in AD. Up until now, the mechanisms underlying the process of Aβ generation and accumulation in the brain have not been well understood. Tyro3 receptor belongs to the TAM receptor subfamily of receptor protein tyrosine kinases (RPTKs). It is specifically expressed in the neurons of the neocortex and hippocampus. In this study, we established a cell model stably expressing APPswe mutants and producing Aβ. We found that overexpression of Tyro3 receptor in the cell model significantly decreased Aβ generation and also down-regulated the expression of β-site amyloid precursor protein cleaving enzyme (BACE1). However, the effects of Tyro3 were inhibited by its natural ligand, Gas6, in a concentration-dependent manner. In order to confirm the role of Tyro3 in the progression of AD development, we generated an AD transgenic mouse model accompanied by Tyro3 knockdown. We observed a significant increase in the number of amyloid plaques in the hippocampus in the mouse model. More plaque-associated clusters of astroglia were also detected. The present study may help researchers determine the role of Tyro3 receptor in the neuropathology of AD.