| First Author | Adelöf J | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 4 | Pages | e13336 |
| PubMed ID | 33720528 | Mgi Jnum | J:304758 |
| Mgi Id | MGI:6693569 | Doi | 10.1111/acel.13336 |
| Citation | Adelof J, et al. (2021) PA28alpha overexpressing female mice maintain exploratory behavior and capacity to prevent protein aggregation in hippocampus as they age. Aging Cell 20(4):e13336 |
| abstractText | With age, protein damage accumulates and increases the risk of age-related diseases. The proteasome activator PA28alphabeta is involved in protein damage clearance during early embryogenesis and has demonstrated protective effects against proteinopathy. We have recently discovered that adult female mice overexpressing PA28alpha (PA28alphaOE) have enhanced learning and memory, and protein extracts from their hippocampi prevent aggregation more efficiently than wild type. In this study, we investigated the effect of overexpressing PA28alpha on aging using C57BL/6NxBALB/c F2 hybrid mice. We found that the hippocampal anti-aggregation effect was maintained in young adult (7 months) to middle-aged (15 months) and old (22 months) PA28alphaOE females. While the PA28alphaOE influence on learning and memory gradually decreased with aging, old PA28alphaOE females did not display the typical drop in explorative behavior-a behavioral hallmark of aging-but were as explorative as young mice. PA28alphaOE lowered PA28-dependent proteasome capacity in both heart and hippocampus, and there was no indication of lower protein damage load in PA28alphaOE. The life span of PA28alphaOE was also similar to wild type. In both wild type and PA28alphaOE, PA28-dependent proteasome capacity increased with aging in the heart, while 26S and 20S proteasome capacities were unchanged in the timepoints analyzed. Thus, PA28alphaOE females exhibit improved hippocampal ability to prevent aggregation throughout life and enhanced cognitive capabilities with different behavioral outcomes dependent on age; improved memory at early age and a youth-like exploration at old age. The cognitive effects of PA28alphabeta combined with its anti-aggregation molecular effect highlight the therapeutical potential of PA28alphabeta in combating proteinopathies. |
