Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders |
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| Institution: | 1. Centro E. Grossi Paoletti, Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milano, Italy;2. Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parma, Italy;3. Dipartimento di Medicina e Chirurgia, Unità di Neuroscienze, Università di Parma, Parma, Italy;1. Physics Institute, Universidad Autónoma de San Luis Potosí, Ave. Dr. Manuel Nava #6, San Luis Potosí SLP 78290, Mexico;2. Department of Physiology and Biophysics, Universidad Autónoma de San Luis Potosí School of Medicine, Ave. V. Carranza 2405, San Luis Potosí SLP 78210, Mexico.;1. Faculty of Pharmaceutical Sciences, Tohoku University, 1-1 Seiryo-machi, Aoba-Ku, Sendai 980-8574, Japan;2. Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan;1. Department of Food Science, Rutgers Center for Lipid Research, Institute of Food Nutrition and Health, Rutgers University, NJ, USA;2. Department of Veterinary Pathobiology, University of Missouri Metagenomics Center, University of Missouri, MO, USA;3. Graduate Program in Endocrinology and Animal Science, Rutgers University, NJ, USA;1. Dipartimento di Scienze degli Alimenti e del Farmaco, Università di Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy;2. Dipartimento di Medicina e Chirurgia, Unità di Neuroscienze, Università di Parma, Via Volturno 39/F, 43125 Parma, Italy;3. Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104, USA |
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| Abstract: | High-density lipoproteins (HDL) play a key role in cholesterol homeostasis maintenance in the central nervous system (CNS), by carrying newly synthesized cholesterol from astrocytes to neurons, to support their lipid-related physiological functions. As occurs for plasma HDL, brain lipoproteins are assembled through the activity of membrane cholesterol transporters, undergo remodeling mediated by specific enzymes and transport proteins, and finally deliver cholesterol to neurons by a receptor-mediated internalization process. A growing number of evidences indicates a strong association between alterations of CNS cholesterol homeostasis and neurodegenerative disorders, in particular Alzheimer's disease (AD), and a possible role in this relationship may be played by defects in brain HDL metabolism. In the present review, we summarize and critically examine the current state of knowledge on major modifications of HDL and HDL-mediated brain cholesterol transport in AD, by taking into consideration the individual steps of this process. We also describe potential and encouraging HDL-based therapies that could represent new therapeutic strategies for AD treatment. Finally, we revise the main plasma and brain HDL modifications in other neurodegenerative disorders including Parkinson's disease (PD), Huntington's disease (HD), and frontotemporal dementia (FTD). |
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