Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms,…

This thesis focuses on amyloid proteins, a class of proteins that convert into amyloid fibrils.

Microglia support the central and peripheral nervous system by forming the first line of defense against hazardous events. Microglia are increasingly acknowledged as critical players in neurodegenerative diseases, highlighting them as potential therapeutic targets.

Lysosomal storage disorders (LSDs) are a group of orphan diseases characterized by lysosomal dysfunction or impaired lysosomal catabolism and affect collectively about 1 in 5000 live births.

Soil is a home for an unbelievable diversity and abundance of microbial life that is essential for supporting life on our planet.

This thesis describes biochemical investigations of glucocerebrosidase (GBA), the lysosomal β- glucosidase that is deficient in Gaucher disease (GD).

Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

Promotor: J. van der Greef; Co-promotor: E. van Wijk, M. Wang

Promotor: J. Kuiper

Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood.

Promotor: Prof.dr. J. Kuiper

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

Ferritin is a spherical metalloprotein, capable of storing and releasing iron in a controllable way. It is composed of a protein shell of about 12 nm and within its cavity, iron is stored in a mineral form.

This thesis explores how electron paramagnetic resonance (EPR) spectroscopy can be used to investigate key biochemical processes.

Promotor: J. van der Greef, T. Hankemeier; Co-promotor: H.A. van Wietmarschen

Promotor: Prof.dr. H.J.M de Groot, Co-Promotor: A. Alia

The emergence of complex diseases resulting from abnormal cell-cell signaling and the spread of infectious diseases caused by pathogens are significant threats to humanity. Unraveling the dynamic mechanisms underlying cell-cell signaling and infectious disease spreading is crucial for effective disease…

In this thesis, two potential therapeutic targets for diabetic nephropathy were dentified and investigated. First, we show that glomerular clusterin is upregulated in diabetic nephropathy and demonstrated that recombinant clusterin protein can protect the podocytes against oxidative stress in vitro.…

Promotor: Prof.dr. H.P. Spaink, Co-promotor: Prof.dr. A.H. Meijer

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The skin is our natural barrier and lipids are a key part of this barrier. In the outer skin layer, the stratum corneum (SC), lipids form a densely organized structure dependent on the composition of these lipids.

The research described in this thesis combines the latest insights in lysosomal function with lysosome centred cell signalling.

Metabolomics is a powerful tool that can provide a comprehensive insight into the complexity of human biology and the pathophysiology of diseases. By analyzing the metabolome, which refers to the complete set of small (endogenous) molecules (with a mass <1500 Da) present within a given biological system,…

Inflammatory skin diseases such as psoriasis and atopic dermatitis can severely impact both the physical and social aspect of a patient’s life. Aberrant inflammatory responses are thought to be a major causative factor in these disorders, but an abundance of different factors contribute to the development…

The ideas underlying this thesis are that lipidomics may improve the diagnosis of liver metabolic diseases, and can provide further insights into the underlying pathophysiology of these diseases.

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In this thesis, we describe the potential of cell mechanical phenotyping for immune cell characterization, diagnosis, drug testing, as well as treatment of disease.

The different kinds of cultural perspectives on health and disease of the participants are related to their knowledge, beliefs, values and practices manifested in various forms of lifestyle in Indonesia. The cultural diversity of the population is also related to differences in health behaviour.

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Promotores: H.A. Udo De Haes, P.M. Brakefield

Psycholoog Bernadet Klaassens heeft een groot fMRI-onderzoek opgezet naar het effect van medicijnen op hersennetwerken bij veroudering en de ziekte van Alzheimer. Het leverde een unieke dataset op en zicht op een nieuwe methode om medicijnen te ontwikkelen voor patiënten met Alzheimer.

Up to 45% of patients with Parkinson's disease experience impulse control disorders, characterised by a loss of voluntary control over impulses, drives or temptations. This study aimed to investigate whether previously identified genetic and psychiatric risk factors interact towards the development…

The progressive loss and degeneration of dopaminergic neurons is a major pathological hallmark of Parkinson's disease (PD). The onset and progression of PD can be triggered by multiple risk factors, for instance, genetic mutation, environmental exposure, and aging.

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Current therapies for patients with atherosclerosis are targeted primarily on reducing blood cholesterol, but this fails to prevent a large number of cardiovascular events.95 In order to identify new therapeutic strategies for treating atherosclerosis, it is important to study the interactions between…

This thesis describes the design and synthesis of novel small molecules based on sulfur-containing heterocycles for the inhibition of glycosidases and glycosyltransferases related to Fabry and Pompe disease.

Within this thesis the central stage is taken by the discovery and investigation of transglycosylation of sterols. First, investigation focuses on the development of a method to accurately detect and quantify glucosylated metabolites in biological materials.

Cardiovascular syndromes are the major cause of death in Western societies.

Promotor: Prof.dr. J. Kuiper

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

The studies described in this thesis deal with glycosidases, in particular alpha-galactosidases.

Cardiovascular diseases are among the most frequent causes of death in the world. The main underlying pathology of cardiovascular diseases is the development of atherosclerosis in the medium and large-sized arteries.

Parkinson's disease is the second most common neurodegenerative disease in the world. One of its symptoms is the loss of dopaminergic neurons in the substantia nigra pars compacta.

Promotores: Prof.dr. J. Kuiper, Prof.dr. P.H.A. Quax, Co-promotor: I. Bot

Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the pa…

Atherosclerosis is the main underlying pathology of cardiovascular disease. Atherosclerosis is caused by an immune response which is directed against (modified) lipoproteins which accumulate in the vessel wall.

According to the amyloid cascade hypothesis, accumulation of beta-amyloid (Aβ) peptides initiates the pathological cascade in Alzheimer's disease (AD).

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