Connection
Search Results to
This is a "connection" page, showing the details of why an item matched the keywords from your search.
One or more keywords matched the following properties of
Mechanisms of virus-induced apoptosis in neurons and CNS
| Property | Value |
|
abstract
|
Central nervous system (CMS) viral infections result from the capacity of viruses to injure neurons and other non-neuronal cells within the brain and spinal cord. A common mechanism by which a diverse group of neurotropic viruses injure target cells in the CMS is through apoptosis. Despite this fact, little is known about the precise mechanisms and specific cellular pathways leading to virus-induced apoptotic neural cell death. In this proposal we will utilize reovirus infection of primary neuronal cultures and a murine model of reovirus- induced encephalitis to examine the cellular pathways involved in virus-induced neuronal apoptosis. We have previously shown that death receptor apoptotic signaling contributes to reovirus-indced neuronal apoptosis. We hypothesize that both mitochondrial and endoplasmic reticulum cell stress apoptotic signaling pathways are also critical to reovirus-induced neuronal cell death. In Aim 1 we will determine the role played by endoplasmic reticulum (ER) and cellular-stress (GADD) pathways on reovirus-induced neuronal apoptosis and characterize the factors involved. In Aim 2 we will determine the role of mitochondria and mitochondrial factors in reovirus-induced apoptosis. Finally, in Aim 3 we will test the effects of manipulating apoptotic pathways on the pathogenesis of reovirus-induced CNS infection in vivo. A key aspect of the proposed studies is the ability to translate results obtained in studies of primary neuronal cultures in vitro, into an in vivo model of CNS viral infection. Reovirus infection was selected for these studies because it is one of the most extensively characterized models of virus-induced apoptosis and offers the advantage of a large pre- existing base of knowledge concerning viral determinants of apoptosis and the cellular pathways involved, as well as an easily accessible in mouse model of CNS apoptosis that allows rapid testing of results obtained in cell culture for their significance on the pathogenesis of CNS viral disease in vivo
|
|
label
|
Mechanisms of virus-induced apoptosis in neurons and CNS
|