Small molecule modulator of aggrephagy regulates neuroinflammation to curb pathogenesis of neurodegeneration.

Background: Plethora of efforts fails to yield a single drug to reverse the pathogenesis of Parkinson's disease (PD) and related α-synucleopathies.

Methods: Using chemical biology, we identified a small molecule inhibitor of c-abl kinase, PD180970 that could potentially clear the toxic protein aggregates. Genetic, molecular, cell biological and immunological assays were performed to understand the mechanism of action.

Fatty acids do not pay the toll: effect of SFA and PUFA on human adipose tissue and mature adipocytes inflammation.

Background: On the basis that high fat diet induces inflammation in adipose tissue, we wanted to test the effect of dietary saturated and polysunsaturated fatty acids on human adipose tissue and adipocytes inflammation. Moreover we wanted to determine if TLR2 and TLR4 are involved in this pathway.

Methods: Human adipose tissue and adipocytes primary cultures were treated with endotoxin-free BSA conjugated with SFA (lauric acid and palmitic acid--LA and PA) and PUFA (eicosapentaeneic acid, docosahexaenoic acid and oleic acid--EPA, DHA and OA) with or without LPS.

Effect of the Cannabinoid Receptor-1 antagonist SR141716A on human adipocyte inflammatory profile and differentiation.

Background: Obesity is characterized by inflammation, caused by increase in proinflammatory cytokines, a key factor for the development of insulin resistance. SR141716A, a cannabinoid receptor 1 (CB1) antagonist, shows significant improvement in clinical status of obese/diabetic patients. Therefore, we studied the effect of SR141716A on human adipocyte inflammatory profile and differentiation.

Effect of apoA-I on cholesterol release and apoE secretion in human mature adipocytes.

Background: The risk of cardiovascular disease is inversely correlated to level of plasma HDL-c. Moreover, reverse cholesterol transport (RCT) from peripheral tissues to the liver is the most widely accepted mechanism linked to the anti-atherosclerotic activity of HDL. The apolipoprotein A-I (apoA-I) and the ABC transporters play a key role in this process.

Signaling pathways involved in LPS induced TNFalpha production in human adipocytes.

Background: The development of obesity has been linked to an inflammatory process, and the role of adipose tissue in the secretion of pro-inflammatory molecules such as IL-6 or TNFalpha has now been largely confirmed. Although TNFalpha secretion by adipose cells is probably induced, most notably by TLR ligands, the activation and secretion pathways of this cytokine are not yet entirely understood. Moreover, given that macrophagic infiltration is a characteristic of obesity, it is difficult to clearly establish the level of involvement of the different cellular types present within the adipose tissue during inflammation.