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Postmortem tissue from patients with neurodegeneration exhibits protein-misfolding stress and reduced proteasome activity. This hallmark burden of proteotoxic stress has led to the term "proteinopathies" for neurodegenerative diseases. Proteinopathies may also be exacerbated by previous insults, according to the two hit hypothesis of accelerated(More)
The two hit hypothesis of neurodegeneration states that cells that have been severely stressed once are more vulnerable to the negative impact of a second hit. In other words, the toxicity of two hits of severe stress may be synergistic in neurons. We previously developed a two hit model of proteotoxic neurodegeneration using the proteasome inhibitor MG132.(More)
In Parkinson's and Alzheimer's diseases, the allocortex accumulates aggregated proteins such as synuclein and tau well before neocortex. We present a new high-throughput model of this topographic difference by microdissecting neocortex and allocortex from the postnatal rat and treating them in parallel fashion with toxins. Allocortical cultures were more(More)
Manual cell counts on a microscope are a sensitive means of assessing cellular viability but are time-consuming and therefore expensive. Computerized viability assays are expensive in terms of equipment but can be faster and more objective than manual cell counts. The present report describes the use of three such viability assays. Two of these assays are(More)
N-Acetyl cysteine, a glutathione precursor, has been shown to benefit patients with Alzheimer's disease and reduce the symptoms of traumatic brain injury in soldiers. Parkinson's and Alzheimer's disease are both characterized by stress from protein misfolding, or proteotoxicity. We have developed a high-throughput model of proteotoxicity by treating(More)
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