As a result of these studies, several signalling pathways including phosphatidylinositol 3-kinase (PI3K)/Akt andtarget of rapamycin (TOR), c-Jun N-terminal kinase (JNK) and bone morphogenetic protein (BMP) signalling, have been shown to be deregulatedin models of proteinopathies, suggesting that two or more initiating events may trigger disease formation in an age-relatedmanner. This evidence concerns the gene MAPK8 and proteostasis deficiencies.