title: Serine phosphorylation and arginine methylation at the crossroads to neurodegeneration.
abstract: Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, polyglutamine diseases and motor neuron diseases, are late-onset and progressive disorders characterized by the accumulation of misfolded proteins inside and outside neurons. No effective therapies exist to delay the onset or arrest the progression of these diseases. One novel and promising therapeutic approach consists of targeting disease-causing proteins at the post-translational level. Here we illustrate this concept using the example of spinal and bulbar muscular atrophy, a neurodegenerative disease caused by polyglutamine expansion in the androgen receptor. Emerging evidence suggests that two key post-translational modifications of polyglutamine-expanded androgen receptor, namely serine phosphorylation by protein kinase B/Akt and arginine methylation by protein arginine methyltransferases, occur at the same consensus site, are mutually exclusive, and have opposing effects on neurotoxicity. Because several proteins linked to neurodegenerative diseases have canonical Akt consensus site motifs, these findings may have a broad impact in the field of neurological diseases caused by misfolded proteins.
authors.affiliation: Laboratory of Transcriptional Neurobiology, Centre for Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy. Electronic address: manuela.basso@unitn.it.
authors.forename: Manuela
authors.initials: M
authors.lastname: Basso
authors.affiliation: Dulbecco Telethon Institute Lab of Neurodegenerative Diseases, Centre for Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy. Electronic address: maria.pennuto@unitn.it.
authors.forename: Maria
authors.initials: M
authors.lastname: Pennuto
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*
chemical_list: D012694:Serine; D001120:Arginine
keywords: Arginine methylation; Neurodegenerative diseases; Protein arginine methyltransferase (PRMT); Protein kinase B (Akt); Serine phosphorylation