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
Reads0
Chats0
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
More filters
Journal ArticleDOI
Unearthing the Janus-face cholesterogenesis pathways in cancer
TL;DR: In this article , the effect of proximal and distal inhibitors of cholesterol biosynthesis against normal and cancer cell growth and metabolism is discussed, and the authors disassociate the two sides of cholesterogenesis, one beneficial to human welfare while the other dysfunctional leading to misery and disease that could result in premature death.
Journal ArticleDOI
MSMO1 deficiency: a potentially partially treatable, ultrarare neurodevelopmental disorder with psoriasiform dermatitis, alopecia and polydactyly.
T Tkemaladze,Eirik Bratland,Kakha Bregvadze,Teona Shatirishvili,Nino Tatishvili,E Abzianidze,Gunnar Houge,Sofia Douzgou +7 more
TL;DR: In this article , the authors describe two siblings from a consanguineous family presenting with novel clinical features of polydactyly, alopecia and spasticity, and they initiated a modified dosage regime with systemic cholesterol supplementation, statins and bile acid along with topical application of a cholesterol/statin formulation.
Journal ArticleDOI
Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases
TL;DR: In this article , the authors provide an overview of the genetic defects associated with lysosomal storage diseases and their impact on the induction of neuro-immune inflammation, and provide new insights into potential biomarkers and therapeutic targets for monitoring and managing the severity of these diseases.
Journal ArticleDOI
Smith-Lemli-Opitz syndrome: A pathophysiological manifestation of the Bloch hypothesis
TL;DR: Smith-Smith-Lemli-Opitz syndrome (SLOS) as discussed by the authors is associated with a defect in the Kandutsch-Russell pathway of cholesterol biosynthesis that results in accumulation of the immediate precursor of cholesterol in its biosynthetic pathway (7-dehydrocholesterol) and an altered cholesterol to total sterol ratio.
Journal ArticleDOI
Cholesterol metabolism pathway in autism spectrum disorder: From animal models to clinical observations
Jaime Lin,Victoria Linden de Rezende,Maiara de Aguiar da Costa,Jade Bittencourt Coutinho de Oliveira,Cinara L. Gonçalves +4 more
TL;DR: In this article , the authors discuss the cholesterol metabolic pathways in the ASD context, as well as in genetic syndromes related to ASD, through clinical observations and animal models, and suggest an important relationship between ASD pathology and cholesterol metabolism impairment; thus, some strategies could be raised at clinical and pre-clinical levels to explore whether cholesterol metabolism disturbance has a generally adverse effect in exacerbating the symptoms of ASD patients.
References
More filters
Journal ArticleDOI
Principles of bioactive lipid signalling: lessons from sphingolipids
TL;DR: An understanding of the complex pathways of sphingolipid metabolism and the mechanisms that regulate lipid generation and lipid action is required to understand the mechanisms of cell growth, death, senescence, adhesion, migration, inflammation, angiogenesis and intracellular trafficking.
Journal ArticleDOI
CNS synaptogenesis promoted by glia-derived cholesterol
Daniela H. Mauch,Karl Nägler,Stefan Schumacher,Christian Göritz,Eva-Christina Müller,Albrecht Otto,Frank W. Pfrieger +6 more
TL;DR: Cholesterol complexed to apolipoprotein E-containing lipoproteins may explain the delayed onset of CNS synaptogenesis after glia differentiation and neurobehavioral manifestations of defects in cholesterol or lipoprotein homeostasis.
Journal ArticleDOI
Tangier disease is caused by mutations in the gene encoding ATP-binding cassette transporter 1
Stephan Rust,Rosier M,Harald Funke,Real J,Amoura Z,Piette Jc,Deleuze Jf,Brewer Hb,Nicolas Duverger,Patrice Denefle,Gerd Assmann +10 more
TL;DR: Tangier disease (TD) was first discovered nearly 40 years ago in two siblings living on Tangier Island This autosomal co-dominant condition is characterized in the homozygous state by the absence of HDL-cholesterol (HDL-C) from plasma, hepatosplenomegaly, peripheral neuropathy and frequently premature coronary artery disease (CAD).
Journal ArticleDOI
The mechanisms of Hedgehog signalling and its roles in development and disease.
TL;DR: Novel biological insights are revealed into the function of HH lipidation in the secretion and transport of this ligand and details of the signal transduction pathway, which involves Patched 1, Smoothened and GLI proteins, as well as, in vertebrates, primary cilia.
Journal ArticleDOI
Binding and Degradation of Low Density Lipoproteins by Cultured Human Fibroblasts COMPARISON OF CELLS FROM A NORMAL SUBJECT AND FROM A PATIENT WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
TL;DR: It is raised that a prerequisite for the regulation of cholestero-genesis in cultured fibroblasts is the initial binding of low density lipoproteins to the high affinity surface receptor sites and that a defect in this process represents the primary genetic abnormality in the disorder familial hypercholesterolemia.