REMOVAGE

Characterization and REMOVal of AGE-associated lipofuscin in neuronal tissues

01.07.2015 bis 30.06.2020

Although it is difficult to entirely separate "healthy" or "normal" aging from early stages of neurodegenerative diseases, one enigmatic phenomenon that is not commonly attributed to any particular disease is the strictly age-associated accumulation of an autofluorescent pigment, termed lipofuscin, in cells of the central nervous system (CNS) comprising neurons
and a particular cell in the back of the eye, retinal pigment epithelial (RPE) cells. It is likely that lipofuscin impairs neuronal function in the aged brain because in two disease conditions the accelerated deposition
of lipofuscin is associated with toxicity: age-related macular degeneration (AMD) where RPE cells die and thereby cannot further protect the retina and genetic forms of massive lipofuscinosis. AMD is a prevalent condition and the most common cause of age-associated blindness in the Western wold. In addition, some mutations associated with neurodegeneration cause lipofuscinosis, for example mutations in the progranulin gene.
Our interdisciplinary consortium of scientists is set to investigate the pathways of lipofuscin generation in the aged CNS by investigating genetic forms of lipofuscinosis. The consortium will also test an availabile drug, Remofuscin, that our group in Tübingen has discovered, and that is able to dissolve lipofuscin from RPE cells, and therefore is a potential remedy for age-associated lipofuscin accumulation.
As a result of the research performed within this project, we will elucidate the molecular mechanisms of lipofuscin generation in the aged CNS and provide a potential pharmacotherapy for lipofuscin deposition
causing the most prevalent form of age-related blindness. Our research will advance a previously underappreciated branch of molecular aging research of the CNS.