Explanipedia

Recombinant cathepsins B and L promote α-synuclein clearance and restore lysosomal function in human and murine models with α-synuclein pathology Open

Denise Balta, Anthony Varghese, Susy Prieto Huarcaya, Alessandro Di Spiezio, André R. A. Marques , et al. · 2025

LIMP-2 deficiency-associated glycolipid abnormalities in mice Open

Paulo Gaspar, André R. A. Marques, Maria J. Ferraz, Markus Daμμe, Gertjan Kramer , et al. · 2025

Glucocerebrosidase (GCase) catalyzes the lysosomal degradation of glucosylceramide (GlcCer). GCase deficiency results in Gaucher disease (GD), a lysosomal storage disorder with characteristic hepatosplenomegaly. Transport of GCase to lysos…

Glucosylated cholesterol accumulates in atherosclerotic lesions and impacts macrophage immune response Open

André R. A. Marques, Inês S. Ferreira, Quélia Ribeiro, Maria J. Ferraz, Elizeth Lopes , et al. · 2025

Cholesteryl Hemiazelate Present in Cardiovascular Disease Patients Causes Lysosome Dysfunction in Murine Fibroblasts Open

Elizeth Lopes, Gisela Machado-Oliveira, Catarina Guerreiro Simões, Inês S. Ferreira, Cristiano Ramos , et al. · 2023

There is growing evidence supporting the role of fibroblasts in all stages of atherosclerosis, from the initial phase to fibrous cap and plaque formation. In the arterial wall, as with macrophages and vascular smooth muscle cells, fibrobla…

Cholesteryl hemiazelate identified in CVD patients causes in vitro and in vivo inflammation Open

Neuza Domingues, Joana Gaifem, Rune Matthiesen, Diana P. Saraiva, Luís Bento , et al. · 2023

Oxidation of PUFAs in LDLs trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of PUFA-esters of cholesterol, the effects of cholesteryl…

Oxidized cholesteryl ester induces exocytosis of dysfunctional lysosomes in lipidotic macrophages Open

Neuza Domingues, André R. A. Marques, Rita Diogo Almeida Calado, Inês S. Ferreira, Cristiano Ramos , et al. · 2023

A key event in atherogenesis is the formation of lipid‐loaded macrophages, lipidotic cells, which exhibit irreversible accumulation of undigested modified low‐density lipoproteins (LDL) in lysosomes. This event culminates in the loss of ce…

A universal GlycoDesign for lysosomal replacement enzymes to improve circulation time and biodistribution Open

Yen‐Hsi Chen, Weihua Tian, Makiko Yasuda, Zilu Ye, Ming Song , et al. · 2023

Currently available enzyme replacement therapies for lysosomal storage diseases are limited in their effectiveness due in part to short circulation times and suboptimal biodistribution of the therapeutic enzymes. We previously engineered C…

Cholesteryl hemiazelate Identified in Cardiovascular Disease Patients Causes<i>in vitro</i>and<i>in vivo</i>Inflammation Open

Neuza Domingues, Joana Gaifem, Rune Matthiesen, Diana P. Saraiva, Luís Bento , et al. · 2023

Oxidation of polyunsaturated fatty acids (PUFA) in low-density lipoproteins (LDL) trapped in the arterial intima plays a critical role in atherosclerosis. Though there have been many studies on the atherogenicity of oxidized derivatives of…

The development of a broad-spectrum retaining β-exo-galactosidase activity-based probe Open

C.J. Kuo, Qin Su, Adrianus M. C. H. van den Nieuwendijk, Thomas J. M. Beenakker, Wendy A. Offen , et al. · 2023

Acid β-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-β-galactosidases involved in lysosomal glycoconjugate metabolism.

Cathepsin D: Analysis of its potential role as an amyloid beta degrading protease Open

Lisa Gallwitz, Lina Schmidt, André R. A. Marques, Andreas Tholey, Liam Cassidy , et al. · 2022

Proteolysis catalyzed by the major lysosomal aspartyl protease cathepsin-D (CTSD) appears to be of pivotal importance for proteostasis within the central nervous system and in neurodegeneration. Neuronal Ceroid Lipofuscinosis (NCL) type 10…

Delay of EGF-Stimulated EGFR Degradation in Myotonic Dystrophy Type 1 (DM1) Open

Eva Alegre-Cortés, Alberto Giménez-Bejarano, Elisabet Uribe-Carretero, Marta Paredes-Barquero, André R. A. Marques , et al. · 2022

Myotonic dystrophy type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the 3′ untranslated region of the dystrophia myotonica protein kinase gene. AKT dephosphorylation and autophagy are associated with DM1. A…

Current methods to analyze lysosome morphology, positioning, motility and function Open

Duarte C. Barral, Leopoldo Staiano, Cláudia G. Almeida, Dan F. Cutler, Emily R. Eden , et al. · 2022

Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essent…

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models Open

Susy Prieto Huarcaya, Alice Drobny, André R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert , et al. · 2022

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggest…

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models Open

Susy Prieto Huarcaya, Alice Drobny, André R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert , et al. · 2022

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggest…

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models Open

Susy Prieto Huarcaya, Alice Drobny, André R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert , et al. · 2022

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggest…

Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models Open

Alice Prieto Huarcaya, Susy Drobny, André R. A. Marques, Alessandro Di Spiezio, Jan Philipp Dobert , et al. · 2022

Parkinson disease (PD) is a neurodegenerative disorder characterized by the abnormal intracellular accumulation of SNCA/α-synuclein. While the exact mechanisms underlying SNCA pathology are not fully understood, increasing evidence suggest…

Cholesteryl hemiazelate causes lysosome dysfunction impacting vascular smooth muscle cell homeostasis Open

Liliana Alves, André R. A. Marques, Nuno Padrão, Filomena A. Carvalho, José Ramalho , et al. · 2021

In atherosclerotic lesions, vascular smooth muscle cells (VSMCs) represent half of the foam cell population, which is characterized by an aberrant accumulation of undigested lipids within lysosomes. Loss of lysosome function impacts VSMC h…

Lysosome (Dys)function in Atherosclerosis—A Big Weight on the Shoulders of a Small Organelle Open

André R. A. Marques, Cristiano Ramos, Gisela Machado-Oliveira, Otília V. Vieira · 2021

Atherosclerosis is a progressive insidious chronic disease that underlies most of the cardiovascular pathologies, including myocardial infarction and ischemic stroke. The malfunctioning of the lysosomal compartment has a central role in th…

GCase and LIMP2 Abnormalities in the Liver of Niemann Pick Type C Mice Open

Martijn J. C. van der Lienden, Jan Aten, André R. A. Marques, Ingeborg S. E. Waas, Per Larsen , et al. · 2021

The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher di…

Human glucocerebrosidase mediates formation of xylosyl-cholesterol by β-xylosidase and transxylosidase reactions Open

Daphne E.C. Boer, Mina Mirzaian, Maria J. Ferraz, Kimberley C. Zwiers, Merel V. Baks , et al. · 2020

Cell Senescence, Multiple Organelle Dysfunction and Atherosclerosis Open

Gisela Machado-Oliveira, Cristiano Ramos, André R. A. Marques, Otília V. Vieira · 2020

Atherosclerosis is an age-related disorder associated with long-term exposure to cardiovascular risk factors. The asymptomatic progression of atherosclerotic plaques leads to major cardiovascular diseases (CVD), including acute myocardial …

The Iminosugar AMP-DNM Improves Satiety and Activates Brown Adipose Tissue Through GLP1 Open

Daniela Herrera Moro Chao, Yanan Wang, Ewout Foppen, Roelof Ottenhoff, Cindy van Roomen , et al. · 2019

Obesity is taking on worldwide epidemic proportions, yet effective pharmacological agents with long-term efficacy remain unavailable. Previously, we designed the iminosugar N-adamantine-methyloxypentyl-deoxynojirimycin (AMP-DNM), which pot…

Enzyme replacement therapy with recombinant pro-CTSD (cathepsin D) corrects defective proteolysis and autophagy in neuronal ceroid lipofuscinosis Open

André R. A. Marques, Alessandro Di Spiezio, Niklas Thießen, Lina Schmidt, Joachim Grötzinger , et al. · 2019

CTSD (cathepsin D) is one of the major lysosomal proteases indispensable for the maintenance of cellular proteostasis by turning over substrates of endocytosis, phagocytosis and autophagy. Consequently, CTSD deficiency leads to a strong im…