| Autor: |
Golomidov IM; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia., Latypova EM; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia., Ryabova EV; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia., Bolshakova OI; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia., Komissarov AE; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia., Sarantseva SV; Petersburg Nuclear Physics Institute named by B.P.Konstantinov of NRC «Kurchatov Institute», Gatchina, Russia. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of neurogenetics [J Neurogenet] 2022 Mar; Vol. 36 (1), pp. 1-10. Date of Electronic Publication: 2022 Apr 25. |
| DOI: |
10.1080/01677063.2022.2064462 |
| Abstrakt: |
Parkinson's disease (PD) is a neurodegenerative disease characterised by the formation of Lewy bodies and progressive loss of dopaminergic (DA) neurons in the substantia nigra. Lewy bodies mainly consist of α-synuclein, which plays a critical role in the pathophysiology of PD. The α-synuclein is encoded by the SNCA gene and is the first identified gene associated with hereditary PD. Currently, there are at least six disease-associated mutations in α-synuclein that cause dominantly inherited familial forms of PD. Targeted expression of human SNCA.WT/SNCA.A30P/SNCA.A53T gene in Drosophila melanogaster over specific times employing a temperature-dependent UAS/GAL4 - GAL80 system allows for the evaluation of neurodegenerative processes. In this study, SNCA was expressed only in the adult stage of Drosophila development for 1 or 2 weeks, followed by repression of gene expression for the rest of the fly's life. It was demonstrated that the level of pathology significantly depends on the duration of α-synuclein expression. SNCA gene expression over a longer period of time caused the death of DA neurons, decreased levels of dopamine and locomotor ability. In this case, the observed neurodegenerative processes correlated with the accumulation of α-synuclein in the Drosophila brain. Importantly, repression of α-synuclein expression led to elimination of the soluble protein fraction, in contrast to the insoluble fraction. No further significant development of characteristic signs of pathology was observed after the α-synuclein expression was blocked. Thus, we suggest that reduction of α-synuclein expression alone contributes to slowing down the development of PD-like symptoms. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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