Oxidative Stress in Neurodegenerative Diseases：氧化应激在神经退行性疾病.ppt

Oxidative Modifications Affect All Cellular Macromolecules Is oxidative stress an early event in AD? In the proposed sequence of degenerative events, it occurs earlier than cytoskeletal alterations. t Accumulation is Associated with a Reduction in Oxidative Stress Antioxidants and anti-inflammatories are protective Antioxidants, including selegiline, lipoic acid, vitamin E, and a diet rich in antioxidants act to protect the body against free radical damage. Studies have shown that these agents may slow the progression of the disease. Women taking estrogen replacement therapy have a decreased risk of AD. Anti-inflammatories, aspirin and ibuprofen, have been proposed to reduce the onset of AD after certain populations that take NSAIDs therapeutically were found to have a lower incidence of dementia. ALCAR, a naturally occurring compound, may help neuron energy production by keeping mitochondria healthy. From: Smith MA, Petot GJ, Perry G. Diet and oxidative stress: a novel synthesis of epidemiological data on Alzheimer’s disease. J Alzheimers Dis 1:203-206, 1999. P. 204. With permission from IOS Press. Sources: 1. Alzheimer’s Disease Statistics Fact Sheet, Alzheimer’s association 1995. 2. Rosenberg et al. National Center for Health Statistics; 1996. Source: Smith MA, Perry G. What are the facts and artifacts of the pathogenensis (sic) and etiology of Alzheimer disease? J Chem Neuroanat 16:35-41, 1998. In vitro modification of NFH and NFM by HNE is dependent upon lysine residues… Levels of HNE do not accumulate with age in the mouse’s sciatic nerve …and phosphorylation state. NFH NFM A B C D Antibody recognition of NFH and NFM (A) is abolished by HNE-lysine (B) but not cyteine (C) or histidine(D). VI. Therapeutics Progression/Incidence Estrogen Acetylsalicylic acid (Aspirin) (-) Deprenyl (selegiline) Ibuprofen Dapsone Acetyl-L-Carnitine (ALCAR) Vitamin E Tenilsetam Antioxidants and anti-inflammatories are protective Diet Lipoic Acid Fru