Neurodegeneration

Research within the Division of Neuropathology is thematically focused on two topics:

 

1. Tauopathies: Mechanisms of Tau aggregation and spreading

Tauopathies represent a heterogeneous group of neurodegenerative diseases comprising e.g. Alzheimer`s disease. Histopathologically, tauopathies feature abnormal intracellular aggregation of the Tau protein. Using murine as well as worm (C. elegans) model systems, we study the molecular mechanisms of Tau aggregation and spreading throughout the nervous system.

 

Recent publications (selected):

  • Hench J et al., A tissue-specific approach to the analysis of metabolic changes in Caenorhabditis elegans. PLOS One, 2011
  • Clavaguera F et al., Brain homogenates from sporadic human tauopathies induce tau inclusions in mouse brain. PNAS, 2013
  • Clavaguera F, Hench J et al., Peripheral administration of tau aggregates triggers intracerebral tauopathy in transgenic mice. Acta Neuropathol, 2014
 

2. Mitochondria and Neurodegeneration

Our lab focuses on the molecular mechanisms of mitochondrial dynamics and their role in neuronal health and pathophysiology. As particularly energy-dependent cells, neurons rely on balanced mitochondrial fusion and fission processes. Using primary neuronal cultures and inducible neuron-specific knockout models of the mitochondrial fission protein DRP1 as experimental tools, we recently found that genetic ablation of mitochondrial fission in forebrain neurons causes defects in synaptic transmission and memory functions. In addition, CNS-specific Drp1 ablation, also activates interorganellar signaling cascades capable of eliciting complex systemic metabolic responses, the biochemical elucidation of which is our current main focus.

 

Recent publications (selected):

  • Ackema K et al., The small GTPase Arf1 modulates mitochondrial morphology and function. EMBO J, 2014
  • Todt F et al., Differential retrotranslocation of Bax and Bak from the mitochondria reveals apoptosis signaling-independent Bax activation. EMBO J, 2015
  • Oettinghaus B et al., Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons. Cell Death Differ, 2016
  • Oettinghaus B et al., Drp1 dependent apoptotic mitochondrial fission occurs independently of Bax, Bak and Apaf1 to amplify cell death by BID and oxidative stress. BBA Bioenergetics, 2016
  • Ackema KB et al., Sar1, a novel regulator of ER-mitochondrial contact sites. PLOS One, 2016
  • Schmitt K et al., Circadian control of Drp1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metabol, 2018
  • Restelli L, Oettinghaus B et al., Neuronal mitochondrial dysfunction activates the integrated stress response to induce fibroblast growth factor 21. Cell Reports, 2018 (in press).
 

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