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ToPAG (Toxic Protein AGreggation in Neurodegeneration) is a new six-year interdisciplinary research project funded by the EU and carried out by two Max-Planck-Institutes. ToPAG’s central focus is neurodegeneration, the progressive loss of structure and function of nerve cells (neurons). Neurodegeneration eventually results in neuronal death, either of motor neurons leading to motor impairment or in central neurons leading to dementia. More than 40 million people worldwide live with dementia, a neurological syndrome which affects memory, thinking and the ability to perform everyday life activities. By 2050, this number is expected to triple. Without effective treatments… 


A human cell line, in which protein aggregates accumulate (green). Aggregates of different sizes can be seen in a many cells. The colour of the nuclei are stained blue.

…especially the industrial countries and their aging populations will face tremendous medical and socio-economic difficulties. Dementia is predominantly caused by different neurodegenerative diseases such as Alzheimer’s or Huntington’s disease. Although the symptoms of neurodegenerative diseases may vary, many of them have one observable feature in common: the accumulation of misfolded proteins inside or outside of neurons (i.e. aggregates).

In order to better understand the formation and effects of these toxic protein aggregates, four leading scientists from the Max Planck Institutes of Biochemistry and Neurobiology in Martinsried near Munich, Germany, have endeavored on a pioneering journey to address this challenge.  They focus on the basic cellular mechanisms of protein aggregate toxicity and establish mouse models to elucidate the role of protein aggregates in neurodegeneration from several different angles using complimentary methods. “By identifying potential drug targets, this information may serve as the basis for developing urgently needed therapies that can halt or reverse disease processes of neurodegeneration”, says Prof. Hartl, the lead investigator of the ToPAG project.