• 2018-07
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  • br Concluding remarks br Definition Prion diseases are fatal


    Concluding remarks
    Definition Prion diseases are fatal neurodegenerative disorders that are caused by an unconventional agent that is neither bacterial nor viral, but is in essence an infectious misfolded amyloidogenic protein, termed a prion (Prusiner, 1982). Once considered highly controversial, the prion hypothesis is now generally accepted and offers a unifying paradigm within which to classify and investigate the disease formerly known as the transmissible spongiform encephalopathies (Table 28.1). The human prion diseases include sporadic, genetic, and acquired disorders. They are characterized neuropathologically by spongiform change in the gray matter with neuronal loss, reactive gliosis, and the accumulation of an abnormal form of prion protein (PrP) in the brain, as typified by Creutzfeldt–Jakob disease (CJD) (Head et al., 2015).
    Classification Classification of human prion diseases has previously been based on clinicopathologic phenotype – CJD, Gerstmann–Sträussler–Scheinker (GSS) disease or fatal familial insomnia (FFI) – and etiology (familial, acquired, sporadic), but classification is increasingly reliant on genetic and molecular criteria, specifically the pathogenic mutations and polymorphisms of PRNP and PrP typing, in combination with the histotyping of neuropathologic lesions in the SB 258719 hydrochloride australia (Head et al., 2015).
    Clinical phenotypes/ neuroimaging correlates
    Diagnostic criteria Human prion diseases benefit from internationally agreed diagnostic criteria that refer to clinical features, duration of illness, the results of clinical investigations (EEG, CSF protein analysis, and MRI), PRNP analysis, and neuropathology to allow suspected cases to be classified as possible, probable, or definite. A definite diagnosis requires neuropathologic confirmation (University of Edinburgh National CJD Research and Surveillance Unit (NCJDRSU), 2017).
    Pathogenesis/experimental models
    Introduction Cell polarity, which is fundamental to many aspects of cell and developmental biology, is involved in the processes of differentiation, proliferation and morphogenesis in both unicellular and multicellular organisms. In a wide range of elementary cellular processes, many constituents of the cell, such as plasma membrane proteins, organelles, and cytoskeletal components are organized asymmetrically within the cell. This asymmetrical pattern of organization is enhanced by cell differentiation processes resulting in dynamic cell compartments specialized in complex vectorial functions. Cell polarity is essential for processes such as the growth of budding yeast [1], cell division [2], the development of a fertilized egg into an organism [3], the transmission of nerve impulses [4], the transport of molecules across an epithelial cell layer [5], cell crawling [6] and lymphocyte homing [7], etc. Transient or stable cell polarization therefore constitutes a universal cellular trait in most multicellular organisms. One of the main challenges arising in this field during the last 15 years has been finding common molecular denominators between all these cellular events and processes, which may look very different in some respects but are all based on the development of cell polarity. Studies on these lines have led to the discovery of three polarity protein complexes that are all essential to epithelial polarity. In this review, it is proposed to report on how these complexes were discovered and to describe the structure of their components, focusing on the mammalian epithelial cells and tight junctions. The polarity of epithelial cells results in the presence of at least two plasma membrane domains: the apical surface facing the external medium and the basolateral surface connected to adjacent cells and connective tissue. The protein and lipid composition of these domains differs, reflecting their specific functions. Tight junctions provide a physical border between apical and lateral domains but their exact role in establishing and/or in maintaining this epithelial cell membrane asymmetry is still under debate. The newly identified partners at work in polarity protein complexes will be reviewed here, as well as the connections between them.