Ricerc@Sapienza

Cholesterol and its oxygenated metabolites, such as oxysterols, are intensively investigated as potential players in the pathophysiology of brain disorder. Altered oxysterol levels have been described in patients with numerous neuropsychiatric disorders, including Alzheimer's disease, Amyotrophic Lateral Sclerosis, Parkinson's disease, X-linked adrenoleukodystrophy, and Smith-Lemli-Opitz Syndrome. Recent studies have shown that Autism Spectrum Disorders are associated with disruption of cholesterol metabolism.

It is now widely accepted that oxysterols are more than metabolic intermediates but are actually bona fide lipid mediators. To qualify as a bona fide lipid mediator, a lipid compound should meet three conditions. First to be endogenous, second to have its levels altered depending on the physiological or pathological situation, and third to induce a signaling response when its levels are altered. As is evident from the papers published in this Special issue, oxysterols largely qualify as bona fide lipid mediators.

The complete mechanism accounting for the progression from simple steatosis to steatohepatitis in nonalcoholic fatty liver disease (NAFLD) has not been elucidated. Lipotoxicity refers to cellular injury caused by hepatic free fatty acids (FFAs) and cholesterol accumulation. Excess cholesterol autoxidizes to oxysterols during oxidative stress conditions. We hypothesize that interaction of FAs and cholesterol derivatives may primarily impair mitochondrial function and affect biogenesis adaptation during NAFLD progression.

Oxysterols, oxidized derivatives of cholesterol found in LDL and atherosclerotic plaques, trigger several biological responses involved in the initiation and progression of atherosclerosis. Endothelial dysfunction, which occurs when vascular homeostasis is altered, plays a key role in the pathogenesis of several metabolic diseases. The contribution of endoplasmic reticulum (ER) stress to endothelial disfunction is a relatively recent area of investigation.

Throughout life, stress stimuli act upon the brain leading to morphological and functional
changes in advanced age, when it is likely to develop neurodegenerative disorders.
There is an increasing need to unveil the molecular mechanisms underlying aging,
in a world where populations are getting older. Egr-1 (early growth response 1), a
transcriptional factor involved in cell survival, proliferation and differentiation – with a role
also in memory, cognition and synaptic plasticity, can be implicated in the molecular

Background and Aims: The activation of human biliary tree stem/progenitor cells (hBTSCs) located in peribiliary glands (PBGs) havebeen recently described in different cholangiopathies, including Primary Sclerosing Cholangitis (PSC) and Cholangiocarcinoma (CCA). In these pathologies, hBTSCs also display features of EMT, senescence and dysplasia. The aim of the present study was to investigate putative agents reproducing in primary cultures of hBTSCs the pathologic features observed in PBGs of human cholangiopathies.