An article showing evidence that faulty autophagic degradation of protein aggregates is the cause of brain damage in certain patients is presented on the cover of the November 5th issue of JCB.
Originally characterized by prof. Per Seglen and his co-workers at the Norwegian Radium Hospital, autophagy is a cellular process that involves the sequestration and degradation of portions of cytoplasm.
Autophagy has recently been shown important for degradation of intracellular protein aggregates that cause brain damage when allowed to accumulate in the central nervous system. Scientists at the CCB therefore investigated whether ESCRT proteins can prevent brain neurodegeneration.
A project group led by researcher Anne Simonsen collaborated with scientists at University College London who have identified mutations in the gene encoding the ESCRT protein CHMP2B in patients suffering from rare, inherited forms of mental retardation.
In an article presented on the cover of the 5th-November issue of Journal of Cell Biology (impact factor 10,152) Simonsen and co-workers show evidence that faulty autophagic degradation of protein aggregates is the cause of brain damage in such patients.
At the same time, a study led by postdoc Tor Erik Rusten in Harald Stenmarks group, published in the 23rd-October issue of Current Biology (impact factor 10,988) shows that fruit flies with reduced levels of ESCRT proteins have impaired autophagy and accumulate protein aggregates that are toxic to nerve cells.
The two articles thus show that ESCRT proteins not only function as tumour suppressors but also to protect against protein aggregate-induced brain damage. This is another example that basic research on one disease may yield results relevant to a completely different group of diseases.
ESCRTs and Fab1 Regulate Distinct Steps of Autophagy.
Rusten TE, Vaccari T, Lindmo K, Rodahl LM, Nezis IP, Sem-Jacobsen C, Wendler F, Vincent JP, Brech A, Bilder D, Stenmark H.
Curr Biol. 2007 Oct 23;17(20):1817-25.
PDF (from Current Biology home page) Abstract (from PubMed)
Tor Erik Rusten (first author)
Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease
Maria Filimonenko, Susanne Stuffers, Camilla Raiborg, Ai Yamamoto, Lene Malerød, Elizabeth M.C. Fisher, Adrian Isaacs, Andreas Brech, Harald Stenmark, and Anne Simonsen
J. Cell Biol. 2007 179: 485-500. Published Nov 5 2007
Abstract (from the JCB home page)
The article is also commented in the "New in the JCB" section:
"Clean up or go crazy" (from "New in the JCB")
Maria Filimonenko (first author)
Autophagy in health and disease - Project group led by Anne Simonsen
Home page of Harald Stenmark's group (radium.no/stenmark)
Centre for Cancer Biomedicine
Department for Biochemistry
Institute for Cancer Research