Investigating protein imbalances in neurodegenerative diseases
Neurodegenerative disorders (NDs) are diseases that affect nerve cells in the spinal cord or brain, causing them to cease functioning or die. They are among the leading causes of death and are projected to become the second leading cause of death in the next 20 years, as populations continue to age. Most NDs show some sort of alteration in proteostasis, the process that regulates the balance of proteins in each cell and an organism overall. These alterations can be imbalances in protein production, irregular sorting or degradation. The secretory and the autophagic pathways are two major regulators of cellular proteostasis, and their crosstalk is likely to be relevant for neurodegeneration. In the EU-funded SAND project, carried out with the support of the Marie Skłodowska-Curie Actions programme, researchers explored these two pathways to understand their impacts in ND. “Our main motivation for focusing on the role of Secretion and Autophagy in Neurodegenerative Disease (SAND) was to increase our knowledge about the mechanisms involved in the development of neurodegenerative disorders, as such knowledge may pave the way for therapeutic targeting,” says Anne Simonsen, head of the Autophagy Lab in the Institute for Cancer Research at Oslo University Hospital. The project created a new training network to help a new generation of researchers acquire the skills needed to investigate proteostasis regulation, to work on tackling the growing threat of ND. The SAND network consists of 15 beneficiaries from 11 countries across Europe, and 12 non-funded partner organisations from 9 countries.
Training early-stage researchers
Fifteen early-stage researchers (ESRs) were recruited through the project, and all were involved in research projects focusing on secretion and/or autophagy. They also participated in various training activities organised by the SAND project. The ESRs also had secondments to other labs within the network or to partner organisations, to strengthen their research and build ties across the community. Specific research objectives included: uncovering the fundamental mechanisms of the autophagy and secretory pathways and their interactions; clarifying how these pathways contribute to NDs; and identifying new drug targets and diagnostic markers for tackling NDs.
Building skills and securing vital results
The SAND network successfully trained a new generation of ESRs in essential scientific and transferable skills for future careers in academia or industry. “SAND ESRs have also obtained results that go beyond the state of the art, identifying new players in autophagy and secretion, mechanisms of protein aggregate formation and new compounds that influence these processes,” adds Simonsen. So far, the results of the project have been published in 25 international peer-reviewed journals, and several manuscripts are in progress. Twelve of the ESRs have defended their thesis or will do so in the spring of 2025, and one will start a PhD in a company within the SAND network this spring.
Progressing Europe’s research into neurodegenerative diseases
The research performed in SAND has led to the discovery of novel regulators of autophagy and secretion, a better understanding of the mechanisms of protein aggregate formation and the development of new cell and animal models to study NDs, as well as the characterisation of chemical compounds that influence autophagy and secretion. “SAND has bridged basic research to translational applications, paving the way for potential new treatments for NDs,” says Simonsen.
Keywords
SAND, neurodegenerative, disease, proteostasis, protein, imbalance, training, network
