Christopher C. Matthews

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Several enzymes with the capacity to degrade glutamate have been suggested as possible neuroprotectants. We initially evaluated the kinetic properties of glutamate pyruvate transaminase (GPT; also known as alanine aminotransferase), glutamine synthetase, and glutamate dehydrogenase under physiologic conditions to degrade neurotoxic concentrations of(More)
A role in neuronal homeostasis is suggested by the persistent expression of the insulin-like growth factors in the adult nervous system. SH-SY5Y human neuroblastoma cells, a well-characterized in vitro model of human neurons, were used to investigate the effects of hyperosmotic stress on neurons. Neuronal DNA fragmentation was detected within 1 h and(More)
Insulin-like growth factor I (IGF-I) and the type I IGF receptor are widely distributed in developing and adult mammalian nervous systems. In vitro, IGF-I is a mitogen for primary neurons and also for cells from the SH-SY5Y human neuroblastoma cell line, a well-characterized model system of neuronal growth. In the current study, we examined the effects of(More)
Previous work in our laboratory demonstrated that a virus could undergo rapid mutation in a host deficient in Se, leading to a normally avirulent virus acquiring virulence due to genome changes. Once these mutations occur, even a host with adequate Se-nutriture is susceptible to the newly virulent virus. What influence does the deficiency in Se have on the(More)
Elimination of glutamate through enzymatic degradation is an alternative to glutamate receptor blockade in preventing excitotoxic neuronal injury. Glutamate pyruvate transaminase (GPT) is a highly active glutamate degrading enzyme that requires pyruvate as a co-substrate. This study examined the ability of GPT to protect neurons of the hippocampal slice(More)
The non-toxin 50 kD C-terminus peptide of the heavy chain of tetanus H(c) contains the ganglioside binding domain of tetanus toxin (TTX). H(c) retains much of the capacity of tetanus toxin for binding internalization and transport by neurons. For this reason tetanus H(c) has been studied as a vector for delivery of therapeutic proteins to neurons. We(More)
There is evidence that raising cellular levels of Cu2+/Zn2+ superoxide dismutase (SOD1) can protect neurons from oxidative injury. We compared a novel method of elevating neuronal SOD activity using a recombinant hybrid protein composed of the atoxic neuronal binding domain of tetanus toxin (C fragment or TTC) and human SOD1 (hSOD1) with increasing cellular(More)
The non-toxic neuronal binding domain of tetanus toxin (tetanus toxin fragment C, TTC) has been used as a vector to enhance delivery of potentially therapeutic proteins to motor neurons from the periphery following an intramuscular injection. The unique binding and transport properties of this 50-kDa polypeptide suggest that it might also enhance delivery(More)
The non-toxic ganglioside binding domain of tetanus toxin (Hc fragment C or TTC) has been studied as a vector for delivering therapeutic proteins to neurons. There is little information on the cellular processing of proteins delivered by linkage to TTC. We have evaluated the cellular handling of a multi-domain hybrid protein containing TTC and both the(More)
The broad-spectrum insecticide rotenone, an inhibitor of complex I of the mitochondrial electron transport chain (ETC), gives rise to oxidative stress and bioenergetic failure. Pesticides including rotenone have been implicated in human neurodegenerative diseases, including Parkinson's disease. Another intensively investigated hypothesis of(More)