January 13, 2014

More than 100 mutations are found in genetic als

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Unformatted text preview: cellular activity and cell death Antioxidant enzymes • Superoxide Dismutase (SOD) – enzymes that catalyze the dismutation of superoxide (O2 ) into oxygen and hydrogen peroxide • SOD1 – localized in cytosol and nucleus and in the intermembrane space of the mitochondria. More than 100 mutations are found in genetic ALS where it shows a toxic gain of function • SOD2 – essential for mitochondrial integrity • SOD3 – low expression profile in the brain SOD superoxide dismutase ( 3 SOD ) enzymes SOD1 its what mutated, it gets toxic gain of its function/ detrimental for the cell Catalase: catalyse decomp of Hydrogen peroxide to water and 02 • Catalase – catalyzes the decomposition of hydrogen peroxide to water and oxygen Mitochondrial dynamics in neurodegeneration Proposed mechanism in AD and PD and ALS Cytochrom c oxidase inhibition in AD. CC can cause cell death/ damage.impaired neuronal Ca detrimental effect on mitochondria. PD -toxic effects in DA neurons/ dysfunction in mitochondria. BCMJ, Vol. 53, No. 4, May 2011 Summary of Oxidative Stress Different ways increase Redox production/protecting against redox production/ Vitamin E/ Co Q,consequences its all these neurodegenerative diseases Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, Second Edition. Edited by Dennis W. Dickson, Roy O. Weller. Common features - Excitotoxicity • Glutamate is an important excitatory neurotransmitter in the CNS and its misregulation has been implicated in over released by neurons can become toxic to cells/ NMDA and AMPA neurodegenerative diseases receptors to allow NA in the cell • Transmission of glutamate is mainly through NMDA and AMPA receptors • Excitotoxicity is caused by excessive synaptic glutamate which causes overactivation of NMDA and AMPA receptors resulting in neuronal death cell death in stroke, ALS AD and PD • Excitotoxicity is involved in cell death in stroke, ALS, AD and PD Text O. Hardiman and C.P. Doherty (eds.), Neurodegenerative Disorders, DOI: 10.1007/978-1-84996-011-3_1, © Springer-Verlag London Limited 2011 Common features - Inflammation • Inflammation is not an initiating factor for neurodegenerative diseases, however, it does contribute to disease progression • Immune system plays essential role in tissue homeostasis and response to infection and injury • Microglia are the resident immune cells in the brain and become a...
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