Neurodegenerative diseases are characterized by the deposition of clumped proteins in the brain and progressive neuronal cell death. Although the causal link between protein aggregates and neurodegeneration is clear, it is still unclear in what way misfolded proteins trigger cell death. A team headed by Professor Jörg Tatzelt, head of the Department of Biochemistry of Neurodegenerative Diseases at Ruhr University Bochum, Germany, showed that misfolded prion proteins can inactivate the TDP-43 protein. TDP-43 is essential for maintaining protein balance in all cell types, especially in nerve cells. A dysfunction of TDP43 is associated with amyotrophic lateral sclerosis and frontotemporal dementia. These findings are crucial for understanding the mechanisms underlying neurodegenerative diseases. The researchers published their results in the journal Brain on 5. September 2023.
Protein aggregates and neurodegeneration
The causes of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia and prion diseases can be many and varied. But there is a common denominator, namely protein misfolding and the occurrence of protein deposits in the brain.
Various approaches and models have shown that misfolded proteins play a crucial role in the disease process. Still, there’s an ongoing debate about the nature of the harmful protein species and how misfolded proteins selectively damage specific neurons.”
Professor Jörg Tatzelt, Head of the Department of Biochemistry of Neurodegenerative Diseases at Ruhr University Bochum, Germany
Studies on genes associated with pathologies have revealed two basic mechanisms by which misfolded proteins can lead to neurodegeneration: Firstly, misfolding can cause the