Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease DOI Creative Commons

Yongmei Wu,

Qiang Guo,

Jinfan Gan

et al.

Brazilian Journal of Medical and Biological Research, Journal Year: 2025, Volume and Issue: 58

Published: Jan. 1, 2025

Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage Parkinson's disease (PD), with axonal degeneration preceding loss cell bodies. Our previous study indicated that dysfunctional retrograde transport could lead death resulting PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as main molecule involved transport, was not affected. This aimed verify hypothesis dynactin rather than dynein may be one key factors PD. Dynactin morpholino used inhibit expression transgenic (Vmat2:GFP) zebrafish, a significant decrease diencephalon dopamine and synuclein aggregation basal plate region. In SH-SY5Y line, dynactin-siRNA knockdown resulted shifting dispersed distribution concentration synapses cytoplasm near axons, fusion rate decreased, especially which blocked α-synuclein autophagy flow. results linked gene dysfunction microtubule system, suggesting contributing

Language: Английский

Dynactin knockdown leads to synuclein aggregation by blocking autophagy in a zebrafish model of Parkinson's disease DOI Creative Commons

Yongmei Wu,

Qiang Guo,

Jinfan Gan

et al.

Brazilian Journal of Medical and Biological Research, Journal Year: 2025, Volume and Issue: 58

Published: Jan. 1, 2025

Axons of dopaminergic neurons projecting from substantia nigra to striatum are severely affected in the early stage Parkinson's disease (PD), with axonal degeneration preceding loss cell bodies. Our previous study indicated that dysfunctional retrograde transport could lead death resulting PD (10.1111/j.1471-4159.2008.05526.x). However, dynein, as main molecule involved transport, was not affected. This aimed verify hypothesis dynactin rather than dynein may be one key factors PD. Dynactin morpholino used inhibit expression transgenic (Vmat2:GFP) zebrafish, a significant decrease diencephalon dopamine and synuclein aggregation basal plate region. In SH-SY5Y line, dynactin-siRNA knockdown resulted shifting dispersed distribution concentration synapses cytoplasm near axons, fusion rate decreased, especially which blocked α-synuclein autophagy flow. results linked gene dysfunction microtubule system, suggesting contributing

Language: Английский

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