Open Close
Reference
Citation
Wang, L., Hagemann, T.L., Kalwa, H., Michel, T., Messing, A., Feany, M.B. (2015). Nitric oxide mediates glial-induced neurodegeneration in Alexander disease.  Nat. Commun. 6(): 8966.
FlyBase ID
FBrf0232410
Publication Type
Research paper
Abstract

Glia play critical roles in maintaining the structure and function of the nervous system; however, the specific contribution that astroglia make to neurodegeneration in human disease states remains largely undefined. Here we use Alexander disease, a serious degenerative neurological disorder caused by astrocyte dysfunction, to identify glial-derived NO as a signalling molecule triggering astrocyte-mediated neuronal degeneration. We further find that NO acts through cGMP signalling in neurons to promote cell death. Glial cells themselves also degenerate, via the DNA damage response and p53. Our findings thus define a specific mechanism for glial-induced non-cell autonomous neuronal cell death, and identify a potential therapeutic target for reducing cellular toxicity in Alexander disease, and possibly other neurodegenerative disorders with glial dysfunction.

PubMed ID
PubMed Central ID
PMC4674772 (PMC) (EuropePMC)
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Commun.
    Title
    Nature communications
    ISBN/ISSN
    2041-1723
    Data From Reference