Oxidative Stress, Antioxidants and Mitophagy

Oxidative stress biochemically hallmarks healthy aging as well as various age-associated neurodegenerative disorders. The accumulation of specific oxidative defects at cellular biomolecules is thought to contribute to the development and progression of age-dependent neurodegenerative diseases. Accordingly, the prevention of oxidation defects is a feasible and straight-forward strategy of nerve cell protection. Furthermore, we are interested in the contribution of mitochondrial dysfunction and degradation mechanisms.

In neurodegenerative disorders cells specifically affected by disease show an elevated oxidative level and a reduced antioxidative defense potential compared to cells from healthy subjects of same age. Enhancement of the physiological antioxidative status of cells, e.g. by antioxidative enzymes or the application of pharmacological antioxidants, leads to life span extension in a number of short-lived organisms. Within our project we are investigating specific features of age-associated modifications of the oxidative status in different brain regions as well as their impact on the development of neurodegenerative diseases. Key aspects are the advancement of novel antioxidants and the characterization of their effect on natural brain aging as well as age-associated neurodegeneration. As experimental paradigms we use primary neuronal cells from animals of different age and various in vivo models, namely C. elegans, M. musculus and R. norvegicus (project headed by Parvana Hajieva).

C.elegans Färbung panneuronal und dopaminerge N.
C.elegans: labeling of dopaminergic neurons (left; dsRed) and pan-neuronal labeling (mid; CFP); right: merge.

A disturbed mitochondrial function was observed in various models of age-associated neurodegenerative disorders. Although the major task of mitochondria is to produce energy by means of oxidative phosphorylation (OXPHOS), they are also involved in a wide variety of essential metabolic and biosynthetic processes. Under physiological conditions mitochondria permanently perform fusion (aggregation) and fission (defragmentation) presumably providing quality control mechanisms. The increased accumulation of mitochondrial defects and the need for increased mitochondrial degradation via the selective autophagic degradation process of mitophagy is one of the putative causes of neurodegenerative disorders. One key aspect in this context are the molecular mechanisms underlying the processes of mitophagy, especially under age- and stress-dependent conditions (project headed by Parvana Hajieva).

Research topics
Link to the German Network for Mitochondrial Disorders
Link mitoNET