Why do our brain become more susceptible to neurodegenerative diseases such as Parkinson's and Alzheimer's as we age?
In a joint project, scientists from the University Medical Center Göttingen (UMG) and the Scripps Research Institute in California, USA, are investigating the role of tiny molecules, so-called microRNAs, which play a decisive role in the development of neurodegenerative diseases such as Parkinson's or Alzheimer's disease. The aim is to find new approaches for the early detection and treatment of these diseases. The research project is funded by the US Chan Zuckerberg Initiative.
The older people get, the more likely they are to develop brain diseases such as Parkinson's or Alzheimer's disease. These diseases are characterized by the death of nerve cells and are therefore also referred to as neurodegenerative diseases. However, it is still unclear which factors are responsible for the death of nerve cells.
Proteins ensure that human cells function and are viable. To do this, the proteins must be produced in the right amount at the right time and folded correctly in order to perform their function. Once they have fulfilled their task, they are broken down and new proteins are formed as required. This process from formation to degradation and the interaction between the individual proteins is a dynamic process that becomes more error-prone with increasing age.
A team of researchers led by Dr. Eugenio F. Fornasiero, group leader at the Department of Neuro- and Sensory Physiology at the University Medical Center Göttingen (UMG), in cooperation with Dr. Giordano Lippi, Associate Professor in the Department of Neuroscience at the Scripps Research Institute, USA, has already shown in previous studies in animal models that some proteins associated with neurodegenerative diseases are no longer exchanged as efficiently in the aged brain. This lack of exchange increases the likelihood of protein accumulation in the brain's nerve cells and possible damage at a molecular level. This happens even before the disease becomes apparent. However, since the protein levels in the brain remain unchanged, mechanisms associated with impaired formation, folding or insufficient degradation of the proteins must play a role. Preliminary results show that tiny molecules, so-called microRNAs (miRNAs), control the production and degradation of certain proteins. The miRNAs are probably crucially involved in maintaining the protein balance in the nerve cells. In older brains, the proteins regulated by miRNAs in particular appear to be insufficiently renewed, which could be due to a misregulation of miRNAs. If the miRNAs do not function properly, the brain can become more susceptible to disease.
Now, the scientists want to build on these findings and find out which of the miRNAs are mainly involved in the development of brain diseases in the joint research project "A neurodegenerative duet: protein turnover and miRNAs". The laboratories of Dr. Fornasiero and Dr. Lippi have developed special genetic and analysis tools to study the miRNAs in detail and to understand how they control the correct exchange of proteins in the brain. "We want to use these investigations to find possible therapeutic approaches to detect neurodegenerative brain diseases at an early stage and treat them more quickly or perhaps even prevent them," says Dr. Fornasiero. The project is funded by the US Chan Zuckerberg Initiative.
The research focus at the UMG is on the investigation of protein stability from living organisms. To this end, samples are currently being collected in which miRNA function is disturbed in both young and old brains. The aim is to understand the fundamental role of miRNAs in regulating the balance between protein production and degradation in the brain. The investigations should also provide insights into how miRNA dysregulation promotes the development of neurodegenerative diseases.
Chan Zuckerberg Initiative
The Chan Zuckerberg Initiative (CZI) was founded in 2015 by Mark Zuckerberg, also founder, chairman and CEO of Meta, and his wife Priscilla Chan to help solve some of society’s toughest challenges — from eradicating disease and improving education, to addressing the needs of our local communities. It is the mission of CZI to build a more inclusive, just, and healthy future for everyone.
Wissenschaftlicher Ansprechpartner:
University Medical Center Göttingen, University of Göttingen
Department of Neuro- and Sensory Physiology
Dr. Eugenio F. Fornasiero
Humboldtallee 23, 37073 Göttingen
Phone + 49 551 / 39-67930
eugenio.fornasiero@med.uni-goettingen.de
Weitere Informationen:
http://fornasierolab.uni-goettingen.de - Fornasiero Lab
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