1,721,644 research outputs found
Dying to survive - Apoptosis, necroptosis, autophagy as the supreme experiments of nature
No full textGuido Kroemer has made fundamental contributions to medical research through his pioneering work in the fields of cell death and cancer research. He is best known for the discovery that the permeabilization of mitochondrial membranes constitutes a decisive step in programmed cell death. Kroemer has explored the fine mechanisms of mitochondrial cell death control, the molecular pathways that explain the inhibition of cell death in cancer cells, upstream of or at the level of mitochondria, and the mechanisms that make cancer cell death immunogenic. Moreover, he discovered the AIF protein and clarified its biological role in apoptosis. His important contributions have been recognized with numerous awards. Kroemer currently serves on more than forty Editorial Boards and is a member of the European Molecular Biology Organization (EMBO), German Academy of Sciences, Austrian Academy of Sciences, European Academy of Sciences (EAS), European Academy of Sciences and Arts (EASA), and European Academy of Cancer Sciences (EACS). He is the President of the European Cell Death Organization (ECDO) and the Founding Director of the European Research Institute for Integrated Cellular Pathology (ERI-ICP). Kroemer is the most cited scientist worldwide in the field of cell death as well as in the area of mitochondrial research
Type 2 transglutaminase in Huntington's disease: A double-edged sword with clinical potential
No full textHuntington's disease (HD) is a dominant genetic neurodegenerative disorder. The pathology affects principally neurons in the basal ganglia circuits and terminates invariably in death. There is compelling necessity for safe and effective therapeutic strategies to arrest, or even retard the progression of the pathogenesis. Recent findings indicate the autophagy-lysosome systems as appealing targets for pharmacological intervention. Autophagy exerts a critical role in controlling neuronal protein homeostasis, which is perturbed in HD, and is compromised in the pathogenesis of several neurodegenerative diseases. Type 2 transglutaminase (TG2) plays an important role both in apoptosis and autophagy regulation, and accumulates at high levels in cells under stressful conditions. TG2 inhibition, achieved either via drug treatments or genetic approaches, has been shown to be beneficial for the treatment of HD in animal models. In this review we will discuss the relevance of TG2 to the pathogenesis of HD, in an effort to define novel therapeutic avenues
The clearance of apoptotic cells in the liver is mediated by the asialoglycoprotein receptor.
No full textA TRIM32-AMBRA1-ULK1 complex initiates the autophagy response in atrophic muscle cells
No full textThe Ser/Thr protein kinase ULK1 is an upstream macroautophagy/autophagy regulator that is rapidly activated to ensure a proper adaptive response to stress conditions. Signaling pathways modulating ULK1 activity have been extensively characterized in response to nutrient/energy shortage, which mainly act by mediating ULK1 post-translational modifications, such as phosphorylation, acetylation and ubiquitination. Less characterized is how tissue-specific stress signals are able to activate ULK1 to induce autophagy. Our recent study has uncovered the E3 ubiquitin ligase TRIM32 as a novel ULK1 activator that regulates autophagy in muscle cells upon atrophy induction. TRIM32 is conveyed to ULK1 by the autophagy cofactor AMBRA1 to stimulate its kinase activity through unanchored K63-linked polyubiquitin chains. Notably, mutations in TRIM32 responsible for limb-girdle muscular dystrophy 2H disrupt its ability to bind ULK1 and to induce autophagy in muscle cells, resulting in a dysregulated activation of the atrophic process. In conclusion, we have identified a novel molecular mechanism by which autophagy is regulated in muscles, whose alteration is associated with the development of muscular dystrophy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Toward the understanding of autophagy regulation and its interplay with cell death pathways.
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