Home Biologist Insight into cellular waste disposal could lead to new treatments for neurodegenerative diseases

Insight into cellular waste disposal could lead to new treatments for neurodegenerative diseases

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A ‘waste collection’ tidies up our cells. If something does not go as planned, serious illnesses such as Alzheimer’s disease or Parkinson’s disease can develop. Molecular biologist Sascha Martens of the University of Vienna and international partners – researchers from the University of Pennsylvania, Monash University, the Max Planck Institute for Biophysics in Frankfurt and UC Berkeley – are studying the associated process: autophagy. Martens and his team recently published new findings on these mechanisms in Nature Communications and The Journal of Biological Chemistry.

Sascha Martens, molecular biologist and subteam leader, University of Vienna.

By studying a tiny mechanism that occurs every millisecond in each of our body cells, an international team of researchers is helping to lay the foundations for the treatment of neurodegenerative diseases. The key process scientists study in this context is the cellular waste disposal system. After all, our cells also produce “waste” all the time.

Autophagy: What to do with waste from our cells?

An elaborate molecular surveillance force identifies suspicious substances – broken cellular components, coagulated proteins or pathogens – and initiates their elimination: they are packed in a “bag” (a double membrane that envelops the waste) and brought to the “bin of recycling” of the cell (the lysosome). There, damaged cellular components are broken down and recycled. This process of cell self-cleaning is called autophagy, which in Greek means “self-devouring”. “And it’s a self-organizing machinery that works perfectly,” says Sascha Martens, molecular biologist and subteam leader at the University of Vienna. He and his colleagues want to understand in detail how molecules cooperate in the production of autophagosomes, because that’s where diseases, ranging from infections to neurodegenerative diseases, can originate.

Drive away Alzheimer’s and Parkinson’s

Alzheimer’s disease often develops in our body for decades without being noticed, until the first symptoms appear and the disease can finally be diagnosed. The tau protein is strongly suspected to cause the most common form of dementia in the world. The protein forms elongated aggregations in our neural cells. These aggregates are generally detected and degraded by the autophagic machinery. This is very similar to Parkinson’s disease, the second disease that Martens’ team is studying in relation to the cellular waste disposal system.

Parkinson’s disease is one of the most common neurodegenerative diseases. Here, an error occurs in the removal of damaged mitochondria – our cells’ energy suppliers – in a specific part of the brain that is responsible for releasing the chemical messenger dopamine. In the long term, this causes the typical symptoms of Parkinson’s disease: patients can no longer control their movements, muscles stiffen and also tremble at rest.

Joining forces

Researchers from the University of Vienna, the University of Pennsylvania, Monash University, the Max Planck Institute for Biophysics in Frankfurt and UC Berkeley decided to join forces to study the disease of Parkinson’s at the cellular level. For their recent project, they received more than $7 million in funding from the Aligning Science Across Parkinson’s Initiative (ASAP), a research network that cooperates with, among others, the Michael J. Fox Foundation.

You could compare it to a band: Some are excellent on guitar and bass, others are drummers or convince with their voice. But the song can only be perfect when played together.”


Sascha Martens, molecular biologist and subteam leader, University of Vienna.

Protein structure experts are based at UC Berkeley’s “Hurley Lab”, cell manipulation happens at Monash University around Michael Lazarou, Erika Holzbaur’s team at the University of Pennsylvania has length advance in neurobiology and researchers under the head of Gerhard Hummer at the Max Planck Institute for Biophysics are preparing models. Sascha Martens and his team at the University of Vienna have specialized in reconstructing the autophagy machinery in the laboratory.

Deciphering the next central steps

Several proteins are involved in the autophagy process. In more than ten years of tedious research, Sascha Martens and his dedicated team managed to isolate dozens of these components and were able to recapitulate the first steps of autophagosome formation. Following the modular principle, they now want to decipher the next central steps of this intelligent machinery that tidies up our cells.

Resume Box Sascha Martens:

After working at the MRC Molecular Biology Laboratory in Cambridge, Sascha Martens came to the University of Vienna in 2009 to study the mechanisms of autophagy in the model organism yeast and in human cells. Sascha Martens is now surrounded by a team of 12 international researchers and has received two ERC grants for his research work.

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Journal references:

  1. Coudevylle, N., et al. (2022) Mechanism of recruitment of Atg9 by Atg11 into the cytoplasm-vacuole targeting pathway. The Journal of Biological Chemistry. doi.org/10.1016/j.jbc.2022.101573.
  2. Turco, E. et al. (2021) Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. Communication Nature. doi.org/10.1038/s41467-021-25572-w.