HCR.20.059 – Neurodegeneration and life-style modulation
Neurological illnesses like e.g. Alzheimer, Parkinson and Huntington disease, are globally becoming more and more prevalent due to e.g. the aging population, and have an immense impact on humanity and society. Although their aetiology is still poorly understood, it is clear that neurodegeneration is an important communality. Key processes like e.g., degeneration of myelin sheets, reduced synaptic transmission, lipid (bi-layer) remodeling, etc. occur simultaneously or sequentially and understanding initiation and progression of these processes potentially direct resolution strategies.
From various fields we see a prominent link between life-style and clinical phenotypess. Hence, life-style intervention programmes, including diets and exercise, offer a window to explore molecular details of clinical symptoms. Moreover, multiple organs show improved conditions upon life-style change. As inactivity seems to be related to initiation of neurological disease, we will explore this field in relation to the recently identified Gut-first and Brain-first phenotypes of Parkinson and in a later stage in Alzheimer and Huntington. We will identify molecular footprints of these phenotypes in in-vitro models, when applicable, and well-established pre-clinical models. We will target brain, muscle and body-fluids, focussing on lipid- and protein-dynamics using stable isotope labelled tracers and State-of-the-Art molecular imaging techniques. Identified markers for the various sub-types, including severity levels, will then be followed during dietary intervention and exercise and linked to pathological changes. Hereafter, we will translate our findings into a clinical setting and confirm their presence and modulation through the life-style change being a dietary change and/or an adapted/different exercise regime. This potentially results in a (partial) treatment for these devastating illnesses through active life-style intervention instead of pharmaceutical treatment associated with potential adverse- or side-effects.
life-style, lipids, Neuro-degeneration, proteins
Erasmus Medical Center (EMC), Free university of Amsterdam, Leiden University (LEI)
|Organisation||Maastricht University (UM)|
|Name||Dr. Rob J. Vreeken|