Alzheimer’s disease, Progressive Supranuclear Palsy, immunoblot
In Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP), the cross-linking of phosphorylated tau into stable insoluble aggregates may lead to formation of paired helical filaments (PHFs) and neurofibrillary tangles (NFTs). NFT pathology is accompanied by oxidative stress in AD and PSP. Previous investigations have uncovered that phosphorylated tau is cross-linked by transglutaminase in the hindbrain of P301L tau transgenic mice. We wanted to determine whether or not P301L mice would exhibit oxidative pathology. To analyze this, we performed immunoblots for the detection of modified carbonyl groups on proteins in spinal cord tissue of P301L tau transgenic, four-repeat wild-type (4RWT) tau, and nontransgenic mice. Carbonyl levels were used as a measure of oxidative stress. We found that P301L tau transgenic mice exhibit more oxidative stress than 4RWT tau and nontransgenic animals. We are currently orally administering cystamine, a transglutaminase inhibitor and antioxidant, to P301L mice. Future investigations will use this immunoblot technique to evaluate the pleiotropic effects of cystamine on P301L mice.
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