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).

Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders / M. Turri, C. Marchi, M.P. Adorni, L. Calabresi, F. Zimetti. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS. - ISSN 1388-1981. - 1867:5(2022 May), pp. 159123.1-159123.14. [10.1016/j.bbalip.2022.159123]

Emerging role of HDL in brain cholesterol metabolism and neurodegenerative disorders

M. Turri
Primo
;
L. Calabresi
Penultimo
;
2022

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).
Alzheimer's disease; Apolipoprotein A-I; Apolipoprotein E; Central nervous system; Cholesterol; High-density lipoproteins; Neurodegenerative diseases;
Settore BIO/14 - Farmacologia
   tArGeting brAIn cholesterol traNSporT in Alzheimer’s Disease (AGAINST-AD)
   AGAINST-AD
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017PFYK27_001
mag-2022
11-feb-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S1388198122000130-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.55 MB
Formato Adobe PDF
1.55 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/917066
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 15
  • ???jsp.display-item.citation.isi??? 15
social impact