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

A proper equilibrium of post-translational protein modifications is essential for normal cell physiology, and alteration in these processes is key in neurodegenerative disorders such as Alzheimer's disease. Recently, for instance, alteration in protein SUMOylation has been linked to amyloid pathology. In this 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. Interestingly, we did not observe any alteration in the levels of SUMO1-conjugation related to Alzheimer's disease. SUMO1 conjugates remained localized to neuronal nuclei upon increased amyloid burden and during aging and were not detected in amyloid plaques. Surprisingly however, we observed age-related alterations in global levels of SUMO1 conjugation and at the level of individual substrates using quantitative proteomic analysis. 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.

Sexually dimorphic effects of oxytocin receptor gene (OXTR ) variants on Harm Avoidance.

BACKGROUND: Recent research has suggested that oxytocin receptor gene (OXTR) variants may account for individual differences in social behavior, the effects of stress and parenting styles. Little is known, however, on a putative role of the gene in heritable temperamental traits. METHODS: We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory. RESULTS: When sex was controlled for and an OXTR genotype*sex interaction term was included in the regression model, 11% of the variance in Harm Avoidance could be explained (uncorrected p ≤ 0.01). Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant. CONCLUSIONS: Findings lend support to a modulatory effect of common OXTR variants on Harm Avoidance in healthy caucasian women and invite resequencing of the gene in anxiety phenotypes to identify more explanatory functional variation.