Alzheimer's World day, 21 September: ERC-funded research

• Important physiological processes such as ageing and pathological mechanisms such as neurodegeneration are dependent on cellular clearance. This process is essential for all cells in all species so that debris accumulated in cells are taken out of the cells to avoid neurodegenerative diseases such as Alzheimer, Huntington or Parkinson. New findings have shown that a gene network named CLEAR controls and regulates cellular clearance. This network could be key to treating neurodegeneration. Combining genomics, bioinformatics, systems biology, chemical genomics, cell biology and mouse genetics, this project will contribute to develop therapies to cure human diseases.
  Researcher: Andrea Ballabio (ERC Advanced Grant 2010), Telethon institute of Genetics and Medicine in Naples, Italy
  Project's title: Modulating cellular clearance to cure human disease (CLEAR)
  Website
• Explaining the basic mechanisms causing Alzheimer's disease
  Remarkable progress has been made in explaining the rare genetic forms of disorders such as Alzheimer. However, the molecular basis of sporadic Alzheimer disease remains largely unresolved and the convergence of several factors must be considered further. This project examines the role of microRNAs (miRNAs) in the normal brain functioning and integrity. miRNAs are molecules which regulate gene expression. When the process is altered, evidence shows that miRNAs can be at the root of the disease, increasing the susceptibility of neurons to Alzheimer. By focusing on three different brain regions, the project will determine which miRNAs are altered in Alzheimer sporadic disease. Experiments on zebrafish and mice will help to determine the functional relevance of miRNAs as well as the networks controlled by miRNAs. Ultimately, the project aims at revealing new insights in the role of miRNAs in the maintenance of brain integrity and to identify new drug targets for treating the disease.
  Researcher: Bart de Strooper (ERC Advanced Grant 2010), Flanders Institute for Biotechnology, Belgium
  Project's title: Role of microRNA dysregulation in Alzheimers disease (MiRNA_AD)
  Website
• The effect of norepinephrine in learning and memory, and its influence on human cognition
  Norepinephrine (NE) is a stress hormone and a neurotransmitter, i.e. a molecule that helps neurons to communicate among themselves. It is released in stressful situations and it regulates blood pressure and heart rate. In parallel, it plays a role in parts of the brain related to attention and learning. In the brain, NE is produced mainly in the region called locus coeruleus (LC). Current theories suggest that the LC-NE system may play a central role in human cognition, as diseases such as Alzheimer show that there can be up to 70% neuronal loss in the LC. However, knowledge about how NE influences cognition is still very scarce. This research project aims to better understand the role of the LC-NE system in human cognition by using brain imaging and pharmacological agents that directly manipulate LC-NE function and measure their effects on brain and behaviour. Results will be critical in elucidating the role of LC-NE function in human attention and performance, and could impact on future studies of clinical disorders, such as Alzheimer’s disease, post-traumatic stress disorder and schizophrenia.
  Researcher: Sander Nieuwenhuis (ERC Starting Grant 2011), Leiden University, The Netherlands
  Project's title: Noradrenergic control of human cognition (NOREPI)
  Website
• Unravelling the dynamics at the origin of Alzheimer
  Accumulation of beta-amyloid peptide forms deposits found in the brains of patients with Alzheimer's disease (AD). These amyloid plaques are thought to play a central role in initiating the disease by damaging the synapses, the structure through which neurones communicate. However, several key questions in this process remain unresolved. This project pursues to correlate structure and function at the level of single synapses in the hippocampus, one of the first regions of the brain to be impaired in AD. Using state-of-the-art techniques such as FRET spectroscopy and high-resolution optical imaging, the research team will elucidate fundamental principles of neuronal circuits function. Results could identify critical steps at the very early stages of "sporadic AD", the most frequent form of the illness.
  Researcher: Inna Slutsky (ERC Starting Grant 2011), Tel Aviv University, Israel
  Project's title: Evolution of Alzheimer's disease: From dynamics of single synapses to memory loss (AβatSynapse)
  Website
   
• Controlling protein damage to better fight neurodegenerative diseases
  This project focuses on uncovering the cellular pathways that regulate toxic protein aggregation (proteotoxicity) to fight aging-associated neurodegenerative diseases such as Alzheimer. The research team recently showed that the gene MOAG-4 (‘modifier of aggregation-4’) plays a key role in the regulation of proteotoxicity during the process of cell ageing. The analysis of MOAG-4 in worm models and of its human counterpart SERF  will offer new starting points to explore age-related, neurodegenerative diseases such as Alzheimer and to look for the development of therapeutic targets in the early molecular stages of these diseases.
  Researcher: Ellen Nollen (ERC Starting Grant 2011), Academisch Ziekenhuis Groningen, The Netherlands
  Project's title: Protein damage control: regulation of toxic protein aggregation in aging-associated neurodegenerative diseases (PDcontrol).
  Website 

More ERC-funded projects in this field (Oktober 2011)
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