title: Molecular chaperones protect against JNK- and Nmnat-regulated axon degeneration in Drosophila.
abstract: Axon degeneration is observed at the early stages of many neurodegenerative conditions and this often leads to subsequent neuronal loss. We previously showed that inactivating the c-Jun N-terminal kinase (JNK) pathway leads to axon degeneration in Drosophila mushroom body (MB) neurons. To understand this process, we screened candidate suppressor genes and found that the Wallerian degeneration slow (Wld(S)) protein blocked JNK axonal degeneration. Although the nicotinamide mononucleotide adenylyltransferase (Nmnat1) portion of Wld(S) is required, we found that its nicotinamide adenine dinucleotide (NAD(+)) enzyme activity and the Wld(S) N-terminus (N70) are dispensable, unlike axotomy models of neurodegeneration. We suggest that Wld(S)-Nmnat protects against axonal degeneration through chaperone activity. Furthermore, ectopically expressed heat shock proteins (Hsp26 and Hsp70) also protected against JNK and Nmnat degeneration phenotypes. These results suggest that molecular chaperones are key in JNK- and Nmnat-regulated axonal protective functions.
authors.affiliation: MRC Centre for Developmental Neurobiology, King's College London, Guy's Campus, London SE1 1UL, UK. andrew.rallis@unice.fr
authors.forename: Andrew
authors.initials: A
authors.lastname: Rallis
authors.forename: Bingwei
authors.initials: B
authors.lastname: Lu
authors.forename: Julian
authors.initials: J
authors.lastname: Ng
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000473:pathology; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism*; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D024521:Mushroom Bodies / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000378:metabolism; D015398:Signal Transduction; D014855:Wallerian Degeneration / Q000378:metabolism* / Q000473:pathology
chemical_list: D029721:Drosophila Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C087442:Hsp26 protein, Drosophila; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D036002:ADP Ribose Transferases; D048670:MAP Kinase Kinase 4; D009612:Nicotinamide-Nucleotide Adenylyltransferase; C583857:Wld(S) protein, Drosophila