Involvement of the lysosomal pathway in neurodegeneration induced by herpes simplex 1 and oxidative stress
Molecular Medicine and Health Biotechnology
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)
DESCRIPTION OF THE OFFER
Alzheimer's disease (AD) is the most common cause of dementia. The majority of AD cases are sporadic and there are numerous risk factors capable of triggering mechanisms leading to brain damage. The understanding of pathogenic mechanisms continues to be a formidable challenge for research, and it is still necessary for the development of better diagnostic methods, which in turn allow to try possible therapeutic interventions, preferably in preclinical stages of AD.
Our research team has been studying the involvement of herpes simplex virus 1 (HSV-1) and oxidative stress (OS) in AD for several years. To do this, we have analysed the effects of both factors on cellular models developed in the laboratory, combining these analyses with genetic association studies to contrast the cell model data with those obtained from the patients. Mounting evidence derived from previous results revealed the ability of HSV-1 and OS to induce the main neurodegeneration markers characteristic of AD (including amyloidogenesis and chnges in tau protein phosphoriylation), and to alter the functionality of the autophagy‑lysosomal system.
Our hypothesis is that alterations of the lysosomal pathway, closely related with cholesterol metabolism, could be involved in the early stages of AD as a primary mechanism of neuronal response to aggressions such as OS, response which would be more intense in neurons sensitized by previous or concomitant challenges such as HSV-1 infections.
To verify the hypothesis, our current aim is to study the mechanisms by wich HSV-1 / OS induce neurodegeneration and lysosomal alterations in neuronal cell models, study in which the Master students will develop their thesis. These cell based experiments will be complemented with the analysis of biochemical and genetic biomarkers related to cholesterol metabolism and the lysosomal pathway, in AD patients.
Biomolecules & Cell D.
María Jesús Bullido