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

Autor: Li J; Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China., Ng KW; Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China., Sung CC; Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China., Chung KKK; Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.
Jazyk: angličtina
Zdroj: Journal of neurochemistry [J Neurochem] 2024 Jul; Vol. 168 (7), pp. 1215-1236. Date of Electronic Publication: 2024 May 01.
DOI: 10.1111/jnc.16122
Abstrakt: 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 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 wild-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 movement dysfunction. Using this model, we were able to monitor the process of α-syn aggregate formation and found a correlation between age and the number and sizes of α-syn aggregates formed. These results provide a potential mechanism by which age-dependent α-syn aggregation may lead to the formation of Lewy bodies in PD pathogenesis.
(© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)
Databáze: MEDLINE
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