Age-associated Diseases

Neurodegenerative diseases are the most prevalent diseases associated with ageing. We explore several different molecular mechanisms contributing to neurodegeneration by spanning a wide methodological range from molecular structures to cognitive parameters in animal models.

• Alzheimer´s disease (Görlach, Greulich, Fändrich*, Kaether, Than)
  structure and function of APP, of γ-secretase-like proteinases and of the presumed signalling complex between APP and Fe65; formation, structure and toxicity of Aβ oligomers and fibrils; role of axonal transport in AD; assembly and transport of γ-secretase; generation of conformation-specific Aβ antibodies

• Impact of thyroid hormones on neuronal function (Heuer)
  role of thyroid hormones in neuronal development and survival; analysis of mice mutants deficient in thyroid hormone transporters such as MCT8

• Myotonic dystrophy and Huntington´s disease (Görlach, Schilling)
  structural analyses of a triplet repeat, causing myotonic dystrophy, by magic-angle-spinning solid state NMR spectroscopy; identification and inhibition of the protease that promotes aggregation of huntingtin through cleavage in a novel recognition site

• Neurodegeneration associated with DNA repair defects (Wang, Görlach)
  impact of mutations in DNA repair genes on brain functions using mouse models; structural analysis of a DNA repair enzyme

• Neurological and cognitive parameters in fish models (Cellerino)
  influence of genetic factors and small molecules

• NF-κB in neurodegeneration and neuroprotection (Weih)
  role of NF-κB transcription factors in exerting negative and positive effects in the nervous system; analyses of ischemic neurodegeneration and axonal regeneration in NF-κB mouse mutants; identification of pro-apoptotic/neuroprotective responses after injury

• Ras signaling in neurons (Morrison)
  role of Ras and Ras-like proteins in various neuronal functions including synaptic structure and plasticity as well as the cellular and molecular basis for learning and memory

* former group