| The physiology of neuroprotection includes the mechanisms and strategies utilized to guard against neuronal injury or degeneration in the central nervous system (CNS). Degenerative disorders may be generally classified as either acute, such as stroke or nervous system injury/trauma or chronic such as Parkinson's (PD) or Alzheimer's (AD) The goal of neuroprotection is to limit neuronal dysfunction and death after such injury and attempt to maintain the highest possible integrity of cellular interactions in the brain resulting in undisturbed neural function. There is a wide range of agents currently under investigation and some can potentially be used in more than one disorder, as many of the underlying mechanisms of damage to neural tissues, in both acute disorders and in chronic neurodegenerative diseases, are similar. These agents include: free radical trappers/scavengers, anti-excitotoxic agents, apoptosis/programmed cell death (PCD) inhibitors, anti-inflammatory agents, and neurotrophic factors. The objective of this research is to characterize a novel family of neuroprotective peptides, teneurin C-terminal associated peptide (TCAP), and to elucidate their protective mechanism.;I have investigated the possibility of TCAP-1 as having the ability to protect neurons during times of pH induced cellular stress due to a decreased incidence of necrosis. I show that TCAP may be upregulating reactive oxygen species (ROS) scavengers to confer neuroprotection during necrotic cell death. I have also shown that TCAP plays a neuroprotective role during apoptotic and glutamate induced stress by decreasing cleavage of death executers and increasing ERK activation and superoxide dismutase. Together, the data indicate that TCAP-1 may play a significant role in preventing neuronal loss in times of neurotoxin stress. Moreover, I have shown that TCAP increases brain derived neurotrophic factor (BDNF) protein and gene expression in cell culture and consequently may confer survivability to cells under stress, thus demonstrating that TCAP may play a pivotal role in maintaining cell viability via modulating growth factor transcription and translation. Thus TCAP-1 may be implicated in activating essential survival pathways leading to the stabilization of the cell. This may prevent neuronal damage caused by neurodegenerative disorders and brain trauma. |
