SUMO1-conjugation is altered during normal aging but not by increased amyloid burden

SUMOylation is a post-translational protein modification that consists of the attachment of a SUMO (small ubiquitin-related modifier) moiety to a lysine residue of a target protein. Alteration in protein SUMOylation has been linked to the amyloid pathology apparent in Alzheimer’s disease. In the present work, we aimed to elucidate the role of protein SUMOylation during aging and increased amyloid burden in vivo using a His6-HA-SUMO1 knock-in mouse in the 5XFAD model of Alzheimer’s disease. We performed anti-HA based affinity purification from young (8 weeks) and old (36 weeks) mouse brains, followed by label-free quantification of purified proteins by LC-MS. Interestingly, we did not observe any alteration in the levels of SUMO1 conjugation related to Alzheimer’s disease, but found age-related alterations in global levels of SUMO1 conjugation. The identified SUMO1 candidate substrates are dominantly nuclear proteins, mainly involved in RNA processing. Our findings open novel directions of research for studying a functional link between SUMOylation and its role in guarding nuclear functions during aging.