Neuroprotective Signal Transduction Pathways of sAPP and TNF

摘要: The pleiotrophic properties of cytokines and soluble growth factors, which tumor necrosis factor (TNF) secreted form amyloid precursor protein (sAPP) are examples, can be appreciated by the variety in vitroneuronal responses to these factors. TNF is mitogenic astrocytes neuronal progenitor cells, neurotoxic oligodendrocytes (1) endothelial cells (2), promotes resistance survival mature neurons (3). Full length βAPP influence cell adhesion via extracellular haparin-binding domains, while sAPP for many nonneuronal (4). amyloidogenic product, Aβ, on other hand, damages kills (5), (6), induces a reactive morphology microglia (7, 8). In light effects neurons, it important dissociate protective pathways from potentially toxic interactions, pharmacological biochemical tools making this distinction possible. Both factors instigate acute (i.e., electrophysiological) long term changes gene expression) relative importance two types still being resolved. For example, we have shown neuroprotective against excitotoxicity mechanism involving long-term (24 hour) exposure (3), studies demonstrated synaptic transmission hippocampal (9), increases after seizure activity animals (10). Combined, indicate that could particular therapeutic disorders such as epilepsy through both upregulation genes. However, if one goal research design regimens mimic or bolster endogenous modes neuroprotection, then elucidation exact either instrumental novel agants.