Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Epicardial Adipose Tissue in Cardiovascular Disease

Cardiovascular disease (CVD) is the maincause of morbidity and mortality in industrialized countries, despite the evolution of treatments and revascularization strategies.Obesity, also accompanied by a chronicinflammatory process, is an independent riskfactor for CVD. Abdominal adipose tissue is acomplex, metabolically very active organcapable of producing different adipokines andhormones, responsible for endocrinemetabolic comorbidities. The epicardial adipose tissue (EAT) has not been as extensivelystudied as the abdominal or subcutaneous adipose tissue. However, recent evidence associates it with an increased cardiometabolic riskdue to its apposition with the heart. EAT storestriglycerides to provide energy to the myocardium and is characterized by its greater ability to release and capture free fatty acids. EATstrategic localization allows a singular crosstalk with cardiomyocytes and vascular wallcells. The fact that EAT produces proinflammatory adipokines as well as metalloproteinases and pro-oxidant substances,highlights its possible direct impact on plaquevulnerability and heart failure, being still necessary further studies of EAT behavior inCVD.Fil: Berg, Gabriela Alicia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Miksztowicz, Verónica Julieta. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Morales, Celina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Barchuk, Magalí. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Transcriptomic and Proteomic Analysis of the Epicardial Adipose Tissue

The study of epicardial adipose tissue (EAT) has been limited by its accessibility due to its proximity to the heart. Moreover, many common animal models do not have EAT, leaving its functional role underestimated and poorly elucidated. Recent advances in medicine and science have allowed for better studies that provide a more comprehensive understanding of its physiological role. One way to dissect its function is the study of its gene expression. In this chapter, we summarize transcriptomic and proteomic analyses which show that EAT expresses a unique set of genes setting it apart from other adipose tissues in the body. This distinctive set of genes modulates a feedback mechanism that has direct interaction with the myocardium. The EAT shares its blood supply with the coronary arteries and innervation with the cardiac muscle, provides physical protection, and regulates energetic metabolites needed by the myocardium. Transcriptomic and proteomic studies show that it is a local source of adipokines with paracrine influence on the myocardium due to the intimate microcirculation shared by both tissues. These analyses also show that it has a role in the immune and endocrine systems affecting the rest of the body. Furthermore, regulation of EAT gene expression is not monolithic and can be affected by multiple factors such as sex, age, underling disease, medication, etc. Gene expression studies can therefore provide great insight into the function of EAT and its role in health and disease

Achievements and obstacles of remyelinating therapies in multiple sclerosis

Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials. However, trial design faces several obstacles: optimal clinical or paraclinical outcome measures to assess remyelination remain ill-defined, and identification of the ideal timing of therapy is also a crucial issue. In addition, realistic expectations are needed concerning the probable benefits of such therapies. Nevertheless, approaches that enhance remyelination are likely to be protective for axons and so could prevent long-term neurodegeneration. Future MS treatment paradigms, therefore, are likely to comprise a combinatorial approach that involves both immunomodulatory and regenerative treatments