Revolutionary research on proteostasis: key against neurodegeneration!

Revolutionary research on proteostasis: key against neurodegeneration!

Heidelberg University has received significant funding for five of its researchers who are pursuing innovative approaches to combat neurodegenerative diseases. Particularly noteworthy is the work of Claudio Joazeiro, whose project “Surveillance of Translation: From Molecular Mechanisms to Roles in Disease” (SuTra) received almost 2.5 million euros from ERC funding. Joazeiro focuses on essential processes of proteostasis, which are essential for cell function and viability.

Proteostasis is a master network that regulates the production, folding, transport and degradation of proteins. A disruption in this complex system can lead to the accumulation of misfolded proteins in nerve cells, which is a key feature of many neurodegenerative diseases, including Alzheimer's, Parkinson's and amyotrophic lateral sclerosis (ALS). Joazeiro investigates specific aspects of ribosome-associated quality control (RQC), a protective mechanism he discovered that is crucial for understanding neurological disorders.

Research on the vulnerability of neuronal cells

In particular, the susceptibility of neurons to RQC defects and their role in the development of neuronal dysfunction are central topics in Joazeiro's research. According to research findings, misfolding and aggregated proteins are common pathological features associated with impaired protein homeostasis. Aging processes also contribute to the accumulation of such defects.

In neurodegenerative diseases, the loss of specific neurons is associated with the aggregations of proteins such as tau in Alzheimer's and α-synuclein in Parkinson's. These aggravations are caused by incorrect protein mode and inconsistent RNA metabolism, which are associated with degenerative neurodegeneration. The ubiquitin-proteasome system (UPS) plays a crucial role here: it tags misfolded proteins for degradation, while autophagy removes larger aggregates and damaged organelles. The improper functioning of these systems leads to toxic accumulations in the neurons.

Therapeutic perspectives

Currently, there are limited therapeutic strategies to combat neurodegenerative diseases. Ingenious approaches targeting multiple disease mechanisms and based on restoring protein function show promising results, but many questions remain unanswered. In the future, disaggregases such as HSP104 could help reverse pathological phase transitions and mitigate neurotoxic effects.

In summary, it is clear that research into proteostasis, and in particular the mechanisms that lead to its dysfunction, is crucial for the development of new therapeutic options to combat neurodegenerative diseases. Joazeiro's work will be instrumental in developing new approaches to targeted therapies and unraveling why neurons are particularly vulnerable to defects in ribosomal quality control. In the long term, this could be crucial for understanding and treating diseases such as Alzheimer's, Parkinson's and ALS.

By specifically studying these biological mechanisms, research expects to not only deepen the understanding of these diseases but also create novel interventions to restore neuronal health.