Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.
Frances M. Platt,Christopher A. Wassif,Alexandria Colaco,Andrea Dardis,Emyr Lloyd-Evans,Bruno Bembi,Forbes D. Porter +6 more
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TLDR
A surprising finding is not only shedding light on details of cellular cholesterol homeostasis but also suggesting novel approaches to therapy.Abstract:
Cholesterol plays a key role in many cellular processes, and is generated by cells through de novo biosynthesis or acquired from exogenous sources through the uptake of low-density lipoproteins. Cholesterol biosynthesis is a complex, multienzyme-catalyzed pathway involving a series of sequentially acting enzymes. Inherited defects in genes encoding cholesterol biosynthetic enzymes or other regulators of cholesterol homeostasis result in severe metabolic diseases, many of which are rare in the general population and currently without effective therapy. Historically, these diseases have been viewed as discrete disorders, each with its own genetic cause and distinct pathogenic cascades that lead to its specific clinical features. However, studies have recently shown that three of these diseases have an unanticipated mechanistic convergence. This surprising finding is not only shedding light on details of cellular cholesterol homeostasis but also suggesting novel approaches to therapy.read more
Citations
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Complex lipid trafficking in Niemann-Pick disease type C.
TL;DR: A reappraisal of lipid storage and lysosomal enzymes activities in tissues/cells from NPC patients and animal models is provided, with emphasis on differences between systemic organs and the brain.
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Emptying the stores: lysosomal diseases and therapeutic strategies
TL;DR: Despite ongoing challenges, various therapeutic strategies for LSDs now exist, with many agents approved, undergoing clinical trials or in preclinical development.
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Diagnostic tests for Niemann-Pick disease type C (NP-C): A critical review.
Marie T. Vanier,Paul Gissen,Paul Gissen,Peter Bauer,Maria Josep Coll,Alberto Burlina,Christian J. Hendriksz,Christian J. Hendriksz,Philippe Latour,Cyril Goizet,Richard W. D. Welford,Thorsten Marquardt,Stefan A. Kolb +12 more
TL;DR: Advances in mass spectrometry has allowed identification of several sensitive plasma biomarkers elevated in NP-C, which, together with the concomitant progress in molecular genetic technology, have greatly impacted the strategy of laboratory testing.
Book ChapterDOI
Laboratory diagnosis of Niemann–Pick disease type C: The filipin staining test
Marie T. Vanier,Philippe Latour +1 more
TL;DR: Methodological caveats and variability of patterns encountered in patients with proven Niemann-Pick C disease (typical "classic" or "intermediate," atypical "variant") are described, leading to a proposed algorithm for interpretation of results in the filipin test.
Journal ArticleDOI
A comparative study on fluorescent cholesterol analogs as versatile cellular reporters
Erdinc Sezgin,Fatma Betul Can,Falk Schneider,Mathias P. Clausen,Mathias P. Clausen,Silvia Galiani,Tess A. Stanly,Dominic Waithe,Alexandria Colaco,Alf Honigmann,Daniel Wüstner,Frances M. Platt,Christian Eggeling +12 more
TL;DR: Different fluorescent lipid analogs are compared for their performance in cellular assays and their applicability in fluorescence correlation spectroscopy (FCS)-based and super-resolution stimulated emission depletion-FCS-based measurements of membrane diffusion dynamics.
References
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Journal ArticleDOI
Recommendations for the diagnosis and management of Niemann-Pick disease type C: an update.
Marc C. Patterson,Christian J. Hendriksz,Mark Walterfang,Frédéric Sedel,Marie T. Vanier,Frits A. Wijburg +5 more
TL;DR: Points of consensus among experts in the diagnosis and treatment of NP-C are reported based on a follow-up meeting in Paris, France in September 2011, providing further information on detection/diagnostic methods, potential new methods of monitoring disease progression, and therapy.
Journal ArticleDOI
Mutations in the Human Sterol Δ7-Reductase Gene at 11q12-13 Cause Smith-Lemli-Opitz Syndrome
Christopher A. Wassif,Cheryl L. Maslen,Stivelia Kachilele-Linjewile,Don S. Lin,Leesa M. Linck,William E. Connor,Robert D. Steiner,Forbes D. Porter +7 more
TL;DR: It is demonstrated that the cDNA that is identified encodes the human sterol Delta7-reductase and that mutations in DHCR7 are responsible for at least some cases of SLOS.
Journal ArticleDOI
Malformation syndromes caused by disorders of cholesterol synthesis
Forbes D. Porter,Gail E. Herman +1 more
TL;DR: In this paper, the authors reviewed clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis and HEM dysplasia.
Journal ArticleDOI
Defective cholesterol biosynthesis in Smith-Lemli-Opitz syndrome.
Mira Irons,Ellen R. Elias,Gerald Salen,Gerald Salen,G.S. Tint,G.S. Tint,AshokK. Batta,AshokK. Batta +7 more
Journal ArticleDOI
Mutations in the Δ7-sterol reductase gene in patients with the Smith–Lemli–Opitz syndrome
Barbara U. Fitzky,Martina Witsch-Baumgartner,Martin Erdel,Joon No Lee,Young Ki Paik,Hartmut Glossmann,Gerd Utermann,Fabian F. Moebius +7 more
TL;DR: The results strongly suggest that defects in the DHCR7 gene cause the Smith-Lemli-Opitz syndrome, where missense mutations reduced heterologous protein expression by >90%.