Research Group Translational Neurodegeneration

Neurodegenerative diseases are age-related, i.e. their incidence rises continually with age. Due to the increasing life expectancy of the population, neurodegenerative diseases will constitute the largest group of age-related diseases alongside tumour diseases and cardiovascular diseases in the future. These diseases cannot yet be cured, and their progression can only be slowed down to a limited extent. Thus, neurodegenerative diseases represent an enormous socio-political and financial challenge for the time to come.

Neurodegenerative diseases are associated with amyloid-like protein aggregation, some of which is entity specific, but the nature of the aggregates and their pathophysiological relevance have not yet been fully clarified. Both nuclear aggregation (e.g. in Huntington's disease) and cytoplasmic aggregation (Alzheimer's, ALS, Parkinson's) are known. This compartment specificity seems to play a crucial role in the pathophysiology, since aggregation in the cytoplasm leads to a disturbance of nucleocytoplasmic protein and RNA transport, while nuclear aggregation does not. These neurodegenerative mechanisms likely also define the selectivity and progression of the various neurodegenerative diseases.

In addition, mechanisms of physiological and/or pathological aging play an important role in the pathophysiology of these diseases. Therefore, three complementary strategies for disease-modifying therapeutic intervention in neurodegenerative diseases are available:

  1. Supporting healthy ageing processes to strengthen physiological resilience (resistance to neurodegenerative insult)
  2. Reduction or deceleration of pathological aging processes
  3. Therapy of the neurodegenerative disease by intervention in its pathophysiology

In fact, a combination of these three strategies offers an attractive solution for the therapy of neurodegeneration, particularly since many mechanisms that are currently believed to be (co-)responsible for neurodegeneration typically increase with age. For example, autophagy becomes ineffective with increasing age; an acceleration of autophagy has been found to prolong life expectancy in mouse models. The same applies to the processes of proteostasis, DNA repair and the entire mitochondrial metabolism.

Disease mechanisms and especially ageing processes are usually examined from the aspect of stressors or degenerative insults. The ability of the organism (or the brain) to resist these factors, i.e. resilience to neurodegenerative or age-related stressors, is attracting increasing attention in research. In the section "Translational Neurodegeneration" the mentioned strategies for a causal therapy of neurodegenerative diseases are further developed and combined in order to achieve a rapid implementation in clinical medicine.

To achieve these goals, the section "Translational Neurodegeneration" uses the entire spectrum of clinical research from fundamental to patient-oriented research.

Research Group Translational Neurodegeneration

Prof. Dr. Dr. Andreas Hermann (AG-Leiter)
Dr. Banaja Dash (PostDoc)
Dr. Hannes Glass (PostDoc)
Dr. Dajana Großmann (PostDoc)
Dr. Christiane Hartmann (PostDoc)
Marcel Naumann (Clinician Scientist)
Dr. Kevin Peikert (Clinician Scientist)
Anna-Maria Pielka (PhD Studentin)
Barbara Szewczyk (PhD Studentin)
Kanza Saleem (PhD Studentin)
Verena Köckritz (med. Doktorandin)
Constantin Minkner (med. Doktorand)
Gretlies Sobiella (med. Doktorandin)
Gael Nils Tarakdjian (med. Doktorand)

Video: Fluorescence live cell imaging of human motor neurons expressing ALS-associated mutant FUS protein tagged with EGFP. Cells were treated with sodium arsenite to induce oxidative stress and stress granules assembly.



Video: Shown is the impact of microtubule disruption (24 hrs Nocodazole, 5µM, mid) or respiratory inhibition (24 hrs Oligomycin A, 10µM, bottom) exclusively at the distal site on the recruitment of WT FUS-GFP to the Laser cut in nuclei (boxed areas) at the proximal seeding site in microfluidic chambers. Note the unaltered FUS recruitment (proximal) despite the severe distal disruption of the mitochondria network along with loss of processive motility in the distally treated cells.