It is likely that pericyte LRP 1 contributes sellckchem to the uptake and processing of amyloid beta peptide and amyloid precur sor protein. Interestingly, accumulation of amyloid beta peptide within the pericyte bodies have been previously described for early onset familial and for spora Inhibitors,Modulators,Libraries dic Alzheimers disease. In line with these observa tions, we analyzed the expression of LRP 1 in brain pericytes during brain inflammation. We demonstrated that the expression of both subunits of LRP 1 is increased in brain pericytes under inflammatory conditions. Conclusions In conclusion, our results as presented here show Inhibitors,Modulators,Libraries that cultured mouse brain pericytes secreting NO, cytokines, and chemokines and responding to LPS stimulation.

Inhibitors,Modulators,Libraries We also showed that pericytes in vitro express LRP 1, an important regulator of the levels of amyloid beta peptide in the brain, and that expression is influenced by LPS. These immunoactive properties of cultured pericytes suggest mechanisms by which they can act as an integral part of the neurovascular unit during brain inflamma tory processes such as brain infections Inhibitors,Modulators,Libraries and neurodegen erative processes. Background The neuropathology of Alzheimers disease is char acterized by the development of extracellular deposits of senile amyloid plaques that are mainly composed of the b amyloid peptide. AD pathogenesis is likely to involve elevated cerebral Ab levels that in turn cause neuroinflammation and neurodegeneration, ultimately leading to dementia through a cascade of neurotoxic events.

Marked by focal activation of microglia and astrocytes in the vicinity of amyloid plaques, AD asso ciated inflammation has been widely described by patho logical examination of brain tissue from AD patients and transgenic mouse models. It has therefore received much attention in the analysis of AD pathologi cal progression. The resulting neuroinflammatory processes Inhibitors,Modulators,Libraries usually involve the release from activated glia of a number of potentially neurotoxic molecules, includ ing reactive oxygen species, nitric oxide, and pro inflam matory chemokines and cytokines such as interleukin 1b, tumor necrosis factor a, and inter feron g. Excessive levels of these mediators are apt to induce neuronal damage through a variety of mechanisms in AD and other neurodegenerative disor ders.

Although the inflammatory processes in AD have been well studied, the amyloidogenic potential of glial cells under pro inflammatory conditions and the mechanisms involved have been relatively unexplored. Neurons are believed to be the major source of Ab in normal and AD brains. Ab is a proteolytic pro duct of amyloid precursor protein resulting from sequential cleavages by the b Vorinostat and g secretase enzymes. The transmembrane aspartic protease BACE1 has been identified as the b secretase and is therefore the key enzyme that initiates Ab peptide gen eration.