			Home About us Contact

Pathological Settings (pathological + setting)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Dissecting the signal transduction pathways triggered by galectin,glycan interactions in physiological and pathological settings

IUBMB LIFE, Issue 1 2010
Diego J. Laderach
Abstract Galectins are a family of evolutionarily conserved animal lectins with pleiotropic functions and widespread distribution. Fifteen members have been identified in a wide variety of cells and tissues. Through recognition of cell surface glycoproteins and glycolipids, these endogenous lectins can trigger a cascade of intracellular signaling pathways capable of modulating cell differentiation, proliferation, survival, and migration. These cellular events are critical in a variety of biological processes including embryogenesis, angiogenesis, neurogenesis, and immunity and are substantially altered during tumorigenesis, neurodegeneration, and inflammation. In addition, galectins can modulate intracellular functions and this effect involves direct interactions with distinct signaling pathways. In this review, we discuss current knowledge on the intracellular signaling pathways triggered by this multifunctional family of ,-galactoside-binding proteins in selected physiological and pathological settings. Understanding the "galectin signalosome" will be essential to delineate rational therapeutic strategies based on the specific control of galectin expression and function. © 2009 IUBMB IUBMB Life, 62(1):1,13, 2010 [source]

Review Article: Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosis

NEPHROLOGY, Issue 5 2010
JINHUA LI
ABSTRACT Diabetic nephropathy (DN) is the most common cause of chronic kidney failure and end-stage renal disease in the Western world. Studies from diabetic animal models and clinical trials have shown that inhibition of the renin-angiotensin system delays the progression of advanced DN. However, a recent large-scale clinical trial has revealed that inhibition of renin-angiotensin system in early phases of DN does not slow the decline of renal function or the development of morphological lesions, suggesting that different mechanism(s) may be involved in the different stages of DN. The role of epithelial-mesenchymal transition in renal fibrosis has been intensively investigated. Recently, endothelial-mesenchymal transition, or endothelial-myofibroblast transition (EndoMT) has emerged as another mechanism involved in both developmental and pathological processes. The essential role of EndoMT in cardiac development has been thoroughly studied. EndoMT also exists and contributes to the development and progression of cardiac fibrosis, lung fibrosis, liver fibrosis and corneal fibrosis. EndoMT is a specific form of epithelial-mesenchymal transition. During EndoMT, endothelial cells lose endothelial markers and obtain mesenchymal markers. Recent evidence from our laboratory and others suggests that EndoMT plays an important role in the development of renal fibrosis in several pathological settings, including experimental DN. This review considers the evidence supporting the occurrence of EndoMT in normal development and in pathology, as well as the latest findings suggesting EndoMT contributes to fibrosis in DN. Whether experimental findings of EndoMT will be reproduced in human studies remains to be determined. [source]

Review: Autophagy in neurodegeneration: firefighter and/or incendiarist?

NEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 5 2009
A. Rami
Autophagy is an intracellular bulk degradation system that is found ubiquitously in eukaryotes. Autophagy is responsible for the degradation of most long-lived proteins and some organelles. Cytoplasmic constituents, including organelles, are sequestered into double-membrane autophagosomes, which subsequently fuse with lysosomes where their contents are degraded. This system has been implicated in various physiological processes including protein and organelle turnover, stress response, cellular differentiation, programmed cell death and pathological conditions. Defects in the autophagy machinery might have several consequences, as they have been associated with neurodegenerative disease and different forms of cancer. Thus, autophagy occupies a crucial position within the cell's metabolism, and its modulation may represent an alternative therapeutic strategy in several pathological settings including stroke, Alzheimer's, Huntington's, Parkinson's diseases and cancer. Recently, research has begun to identify some characteristics of neuronal autophagy. The results suggest that autophagy may provide a neuroprotective mechanism. However, there is evidence showing that dysfunction of autophagy in certain pathological situations can trigger and mediate programmed cell death. Autophagy has also been defined as prime suspect cause of non-apoptotic cellular demise. However, there is now mounting evidence that autophagy and apoptosis share several common regulatory elements that are crucial in any attempt to understand the dual role of autophagy in cell death and cell survival. It will be of fundamental importance to dissect whether autophagy is primarily a strategy for survival or whether autophagy can also be a part of a cell death programme and thus contribute to cell death. Many questions are open. Is autophagy a direct death execution pathway? Is autophagy an innocent bystander? Is autophagy a defence mechanism or just a scavenger or self-clearance tool in the cell? A profound understanding of the biological effects and the mechanisms underlying autophagy in neurones might be helpful in seeking effective new treatments for neurodegenerative diseases. Here, we review the defining characteristics of autophagy with special attention to its role in neurodegenerative disorders, and recent efforts to delineate the pathway of autophagic protein degradation in neurone. [source]