LRRK2 and neuroinflammation: Partners in crime in Parkinson's disease?

3noopenopenRusso, Isabella*; Bubacco, Luigi; Greggio, ElisaRusso, Isabella; Bubacco, Luigi; Greggio, Elis

Nuclear-cytoplasmic Shuttling in Chronic Myeloid Leukemia: Implications in Leukemia Maintenance and Therapy

Nuclear-cytoplasmic shuttling is a highly regulated and complex process, which involves both proteins and nucleic acids. Changes in cellular compartmentalization of various proteins, including oncogenes and tumor suppressors, affect cellular behavior, promoting or inhibiting proliferation, apoptosis and sensitivity to therapies. In this review, we will recapitulate the role of various shuttling components in Chronic Myeloid Leukemia and we will provide insights on the potential role of shuttling proteins as therapeutic targets

PCSK9 Biology and Its Role in Atherothrombosis

It is now about 20 years since the first case of a gain-of-function mutation involving the as-yet-unknown actor in cholesterol homeostasis, proprotein convertase subtilisin/kexin type 9 (PCSK9), was described. It was soon clear that this protein would have been of huge scientific and clinical value as a therapeutic strategy for dyslipidemia and atherosclerosis-associated cardiovascular disease (CVD) management. Indeed, PCSK9 is a serine protease belonging to the proprotein convertase family, mainly produced by the liver, and essential for metabolism of LDL particles by inhibiting LDL receptor (LDLR) recirculation to the cell surface with the consequent upregulation of LDLR-dependent LDL-C levels. Beyond its effects on LDL metabolism, several studies revealed the existence of additional roles of PCSK9 in different stages of atherosclerosis, also for its ability to target other members of the LDLR family. PCSK9 from plasma and vascular cells can contribute to the development of atherosclerotic plaque and thrombosis by promoting platelet activation, leukocyte recruitment and clot formation, also through mechanisms not related to systemic lipid changes. These results further supported the value for the potential cardiovascular benefits of therapies based on PCSK9 inhibition. Actually, the passive immunization with anti-PCSK9 antibodies, evolocumab and alirocumab, is shown to be effective in dramatically reducing the LDL-C levels and attenuating CVD. While monoclonal antibodies sequester circulating PCSK9, inclisiran, a small interfering RNA, is a new drug that inhibits PCSK9 synthesis with the important advantage, compared with PCSK9 mAbs, to preserve its pharmacodynamic effects when administrated every 6 months. Here, we will focus on the major understandings related to PCSK9, from its discovery to its role in lipoprotein metabolism, involvement in atherothrombosis and a brief excursus on approved current therapies used to inhibit its action

sodium azide in commercially available c reactive protein preparations does not influence matrix metalloproteinase 2 synthesis and release in cultured human aortic vascular smooth muscle cells

Detection of circulating concentrations of the acute-phase reactant C-reactive protein (CRP), which is synthesized in response to proinflammatory cytokines, is a relevant tool for identifying the involvement of low-grade inflammation in atherosclerosis and for predicting future atherothrombotic events (1). Whether CRP is only a marker or is also an active player in atherosclerotic injury is a matter of intense debate (2). CRP is present in atherosclerotic lesions (3) and can contribute directly to atherothrombosis (4). In particular, CRP induces expression of proatherogenetic molecules in endothelial cells and promotes LDL uptake by macrophages (4). We recently observed that CRP increases synthesis and secretion of matrix metalloproteinase 2 (MMP-2) from cultured human vascular smooth muscle cells (hVSMCs) (5), a mechanism potentially involved in plaque destabilization. Recently, however, the reliability of results concerning CRP obtained in vitro has been

Learning online: Remote teaching and university student’s engagement

The COVID-19 pandemic has had a dramatic impact on many dimensions of living and working conditions, and uncertainties about the developments that we shall still face in the near future. This paper analyses the implications of a forced overnight push to online teaching. Drawing upon an online survey conducted during the 2020 lockdown by the University of Modena and Reggio Emilia, this article describes students' living and studying conditions revealed by a large set of open and closed questions. The survey provides significant information on the students' real off-campus conditions, crucial data for the multidimensional analysis by combining non-parametric multivariate analysis of closed questions with textual analyses. It offers important indications about the most useful tools for inclusive teaching across thematic areas and highlights the main difficulties that emerged during the lockdown. Reflections on advantages and disadvantages, strengths and weaknesses in the innovative learning environment set up overnight are offered at a policy level