The role of age ‐associated alpha‐synuclein aggregation in a conditional transgenic mouse model of Parkinson's disease: Implications for Lewy body formation

In this study, we found that a selective expression of WT (WT-α-syn) or a modified form of α-syn (WT-α-ayn-CL1) which has an increased propensity for aggregation in the dopaminergic neurons could lead to an age-dependent neurodegeneration. We further f ound that accumulation of alpha-syn aggregates in sizes and numbers were age-associated, suggesting a possible mechanism in the formation of Lewy bodies and neurodegeneration in PD. AbstractParkinson'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 α-synuclein (α-syn), a major component of Lewy bodies, which are a classical pathological hallmark of PD. These findings suggest that α-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 w ild-type (WT) α-syn or a mutant form with an increased propensity to aggregate, designated as WT-CL1 α-syn, could be used to study how α-syn aggregation contributes to PD. In this study, we established a transgenic mouse model that conditionally expresses WT or WT-CL1 α-syn in dopaminergic (DA) neurons and found that the expression of either WT or WT-CL1 α-syn was associated with an age-dependent degeneration of DA neurons and...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research