just what is "Cell Cycle Dysfunction" and how does it cause AZ
http://www.amarantus.com/science/cell-cycle-dysfunction
Dr. Thomas Arendt - LymPro founder & pioneer
http://www.researchgate.net/publication/65658...plasticity
ABSTRACT Higher cerebral functions are based upon a dynamic organization of neuronal networks. To form synaptic connections and to continuously re-shape them in a process of ongoing structural adaptation, neurons must permanently withdraw from the cell cycle. In other words, synaptic plasticity can only occur on the expense of the ability to proliferate. Previously, we have put forward a hypothesis, coined "Dr. Jekyll and Mr. Hyde concept" that differentiated neurons after having withdrawn from the cell cycle are able to use those molecular mechanisms primarily developed to control proliferation alternatively to control synaptic plasticity [T. Arendt, Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways The Dr. Jekyll and Mr. Hyde Theory of Alzheimer's disease or The yin and yang of Neuroplasticity. Progr. Neurobiol. 71 (2003) 83-248]. The existence of these alternative effector pathways within a neuron might put it on the risk to erroneously convert signals derived from plastic synaptic changes into cell cycle activation which subsequently leads to cell death. Here we add further evidence to this hypothesis demonstrating a tight association of the origin recognition complex (ORC) with neurofibrillar pathology in AD. The ORC is a critical "guard" of DNA replication and point of convergence of numerous functionally redundant signaling pathways involved in cell cycle progression and transcriptional silencing of apoptotic programmes. ORC subunits in the mammalian brain and their homologes in Drosophila, however, have further been implicated in the regulation of structural neuronal plasticity and cognitive function. We propose that the abnormal subcellular distribution and segregation of ORC proteins in AD might compromise their physiological function in gene silencing and plasticity. This might result in cell cycle activation, DNA-replication and de-repression of apoptotic programmes. ORC subunits might, thus, provide a direct molecular link between synaptic plasticity, DNA replication and cell death.
Dr. Thomas Arendt is Professor of Neuroscience and runs the Paul Flechsig Institute of Brain Research, which is a Research Institute of Leipzig University with about 50 staff members. He is also the Director of the Alzheimer Centre Leipzig and Director of the Interdisciplinary Centre for Clinical Research Leipzig. He has over 30 years of experience in R&D of therapeutic and diagnostic strategies of neurodegenerative disorders and has made several seminal contributions to therapeutic concepts of Alzheimer´s disease, including stem cell therapy and modulating tumor suppressor genes. He has published work in top-ranked journals, including Cell, Nature, J.Cell Biol., J. Neurosci., and holds several patents for CNS diagnostics and treatment with some of them out-licensed to biotech companies in the United States. Over the last 30 years, his research has continuously been funded by the German Research Foundation, German Federal Ministry for Education and Research, European Commission and others. In the early eighties of the 20th century, he was involved in identifying the degeneration of the cholinergic system in Alzheimer´s disease laying the basis for todays´ only available treatments. He is one of the pioneers of the "cell-cycle theory" of Alzheimer´s disease which he developed further towards a diagnostic and therapeutic concept.
http://www.amarantus.com/science/cell-cycle-dysfunction
Dr. Thomas Arendt - LymPro founder & pioneer
http://www.researchgate.net/publication/65658...plasticity
ABSTRACT Higher cerebral functions are based upon a dynamic organization of neuronal networks. To form synaptic connections and to continuously re-shape them in a process of ongoing structural adaptation, neurons must permanently withdraw from the cell cycle. In other words, synaptic plasticity can only occur on the expense of the ability to proliferate. Previously, we have put forward a hypothesis, coined "Dr. Jekyll and Mr. Hyde concept" that differentiated neurons after having withdrawn from the cell cycle are able to use those molecular mechanisms primarily developed to control proliferation alternatively to control synaptic plasticity [T. Arendt, Synaptic plasticity and cell cycle activation in neurons are alternative effector pathways The Dr. Jekyll and Mr. Hyde Theory of Alzheimer's disease or The yin and yang of Neuroplasticity. Progr. Neurobiol. 71 (2003) 83-248]. The existence of these alternative effector pathways within a neuron might put it on the risk to erroneously convert signals derived from plastic synaptic changes into cell cycle activation which subsequently leads to cell death. Here we add further evidence to this hypothesis demonstrating a tight association of the origin recognition complex (ORC) with neurofibrillar pathology in AD. The ORC is a critical "guard" of DNA replication and point of convergence of numerous functionally redundant signaling pathways involved in cell cycle progression and transcriptional silencing of apoptotic programmes. ORC subunits in the mammalian brain and their homologes in Drosophila, however, have further been implicated in the regulation of structural neuronal plasticity and cognitive function. We propose that the abnormal subcellular distribution and segregation of ORC proteins in AD might compromise their physiological function in gene silencing and plasticity. This might result in cell cycle activation, DNA-replication and de-repression of apoptotic programmes. ORC subunits might, thus, provide a direct molecular link between synaptic plasticity, DNA replication and cell death.
Dr. Thomas Arendt is Professor of Neuroscience and runs the Paul Flechsig Institute of Brain Research, which is a Research Institute of Leipzig University with about 50 staff members. He is also the Director of the Alzheimer Centre Leipzig and Director of the Interdisciplinary Centre for Clinical Research Leipzig. He has over 30 years of experience in R&D of therapeutic and diagnostic strategies of neurodegenerative disorders and has made several seminal contributions to therapeutic concepts of Alzheimer´s disease, including stem cell therapy and modulating tumor suppressor genes. He has published work in top-ranked journals, including Cell, Nature, J.Cell Biol., J. Neurosci., and holds several patents for CNS diagnostics and treatment with some of them out-licensed to biotech companies in the United States. Over the last 30 years, his research has continuously been funded by the German Research Foundation, German Federal Ministry for Education and Research, European Commission and others. In the early eighties of the 20th century, he was involved in identifying the degeneration of the cholinergic system in Alzheimer´s disease laying the basis for todays´ only available treatments. He is one of the pioneers of the "cell-cycle theory" of Alzheimer´s disease which he developed further towards a diagnostic and therapeutic concept.
