REACTIVE OXYGEN SPECIES INDUCED NEURODEGENERATION IN ALZHEIMER'S DISEASE

Oxidative stress is caused by an imbalance between the prooxidant and antioxidant systems. In neuropathology of Alzheimer's disease the important markers of oxidative stress in brain are senile plaques, neurofibrillary tangles, protein and nucleic acid oxidation, lipid peroxidation and mitochondrial abnormalities. Amyloid - beta aggregates deposition in brain induces oxidative changes and generation of an oxidative microenvironment. The increased levels of soluble amyloid - beta(1-42) oligomers lead to neurodegeneration, memory deficits and loss of connectivity by causing aberrations in synapse composition, synapse and dendritic loss and abnormalities. Amyloid - beta proteins and mitochondrial oxidative stress cause hyperphosphorylation of tau protein. Soluble hyperphosphorylated tau oligomers disrupt synaptic function and are involved in synapse loss. For pharmacological treatment of Alzheimer's disease the most important drug discovery strategies include application of antioxidants and inhibitors of acethylcholinesterase, gamma - secretase and aggregation of tau protein.