| First Author | Li J | Year | 2024 |
| Journal | J Neurochem | Volume | 168 |
| Issue | 7 | Pages | 1215-1236 |
| PubMed ID | 38693066 | Mgi Jnum | J:353925 |
| Mgi Id | MGI:7716552 | Doi | 10.1111/jnc.16122 |
| Citation | Li J, et al. (2024) The role of age-associated alpha-synuclein aggregation in a conditional transgenic mouse model of Parkinson's disease: Implications for Lewy body formation. J Neurochem 168(7):1215-1236 |
| abstractText | Parkinson's disease (PD) is a common neurodegenerative disorder that is affecting an increasing number of older adults. Although PD is mostly sporadic, genetic mutations have been found in cohorts of families with a history of familial PD (FPD). The first such mutation linked to FPD causes a point mutation (A53T) in alpha-synuclein (alpha-syn), a major component of Lewy bodies, which are a classical pathological hallmark of PD. These findings suggest that alpha-syn is an important contributor to the development of PD. In our previous study, we developed an adenoviral mouse model of PD and showed that the expression of wild-type (WT) alpha-syn or a mutant form with an increased propensity to aggregate, designated as WT-CL1 alpha-syn, could be used to study how alpha-syn aggregation contributes to PD. In this study, we established a transgenic mouse model that conditionally expresses WT or WT-CL1 alpha-syn in dopaminergic (DA) neurons and found that the expression of either WT or WT-CL1 alpha-syn was associated with an age-dependent degeneration of DA neurons and movement dysfunction. Using this model, we were able to monitor the process of alpha-syn aggregate formation and found a correlation between age and the number and sizes of alpha-syn aggregates formed. These results provide a potential mechanism by which age-dependent alpha-syn aggregation may lead to the formation of Lewy bodies in PD pathogenesis. |
