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Aging during aging increased oxidative stress

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Unformatted text preview: s and could be targeted for diagnosis and therapy Neurodegeneration vs. aging • During aging • Increased oxidative stress • Perturbed energy homeostasis • Accumulation of damaged proteins • Lesions in cells nucleic acids Acceleration of things that Are already happening. Healthy control, we have accumulation of aggregations. • Changes are exacerbated in vulnerable populations of neurons in neurodegenerative disorders • Neurodegenerative disorder occurring depends on • Genetic factors • Environmental factors Genetically predisposed to have or not have disorder. less likely to get a certain disorder. your genetic play huge role.Environmtal factors.Can cause disruption in the body. Mitochondrial dysfunction/ protein misfolding/ oxidative stress.. all these come together to cause a disease all these things increase your chances of getting disorder Common features • Neurodegenerative diseases share the common property of loss of specific populations of neurons • The particular system affected determines the clinical presentation • It remains one of the major unattained goals of modern research on the degenerative diseases to determine the molecular basis for selective vulnerability Who, where and when of neuronal death in neurodegenerative diseases Start at Hippocampus blue onset occurs with AD PD substantia nigra.Late onset in the 7th decade. HD its really in basal ganglia, striatum ,GABA inhibitory • DA neurons in PD • Motor neurons in ALS • Cholinergic and glutamatergic neurons in AD Text • GABA inhibitory neurons in HD Text Nature Reviews Neuroscience 2006 7:278-294 Common Features in Neurodegeneration • Increased cell death • Protein misfolding and aggregation in the intracellular or extracellular matrix what is happening to the neurons ? Increase cell death mitochondrial dysfunction/ excitoxicity/ inflammaton • Mitochondrial dysfunction, increased oxidative stress and production of ROS • Excitotoxicity • Inflammation Common features - Cell death • Three major morphological types of cell death have been described: • Apoptosis • Necrotic cell death • Autophagic cell death We lose neurons. Cell can die by apoptosis Necrotic cell death Degeneration in cortical neurons Normal Degenerating Dead Cell dies ,it starts have a different shape, degenerating, starts dying , condensing ,we cant see the cells anymore Journal of Cerebral Blood Flow & Metabolism (2011) 31, 328–338 Common features - Cell death • Apoptosis - characterized by chromatin condensation, n...
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