The increase of α-synuclein and alterations of dynein in A53T transgenic and aging mouse

Wang, Yiqing; Sun, Zhipeng; Du, Shouyun; Wei, Hongyu; Li, Xiuming; Li, Xiaojing; Shen, Jian; Chen, Xinya; Cai, Zenglin

doi:10.1016/j.jocn.2021.11.002

Cited by 6 publications

(2 citation statements)

References 52 publications

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“…Moreover, α-Syn aggregates reduced the retrograde transport of LC3+ autophagosomes, Rab7+ and TrkB+ endosomes in rat primary midbrain neurons ( Volpicelli-Daley et al, 2014 ; Koch et al, 2015 ), which is jointly mediated by a transport complex formed by dynein, DCTN1 and snapin under physiological conditions. Though upregulation of dynein expression perhaps reflect its enhanced function at early stage of PD ( Steinberg, 2011 ), promoting protein aggregates clearance ( Ripon et al, 2020 ), α-Syn aggregates may interfere with partial retrograde processes via affecting the formation of dynein transport complexes, disturbing extracellular signaling and activity of mitophagy ( Volpicelli-Daley et al, 2014 ; Koch et al, 2015 ; Boecker et al, 2021 ; Wang et al, 2022 ). Recent studies did not reveal a direct effect of α-Syn aggregation on the reduced expression of dynein, and the changes on levels of dynein possibly due to diffused neurodegeneration at late stage of PD.…”

Section: Axonal Transport Defects In Neurodegenerative Diseasesmentioning

confidence: 99%

Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Yang

Lian

et al. 2023

Front. Mol. Neurosci.

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Many neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are characterized by the accumulation of pathogenic proteins and abnormal localization of organelles. These pathological features may be related to axonal transport deficits in neurons, which lead to failures in pathological protein targeting to specific sites for degradation and organelle transportation to designated areas needed for normal physiological functioning. Axonal transport deficits are most likely early pathological events in such diseases and gradually lead to the loss of axonal integrity and other degenerative changes. In this review, we investigated reports of mechanisms underlying the development of axonal transport deficits in a variety of common neurodegenerative diseases, such as Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson’s disease and Huntington’s disease to provide new ideas for therapeutic targets that may be used early in the disease process. The mechanisms can be summarized as follows: (1) motor protein changes including expression levels and post-translational modification alteration; (2) changes in microtubules including reducing stability and disrupting tracks; (3) changes in cargoes including diminished binding to motor proteins. Future studies should determine which axonal transport defects are disease-specific and whether they are suitable therapeutic targets in neurodegenerative diseases.

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Section: Axonal Transport Defects In Neurodegenerative Diseasesmentioning

confidence: 99%

Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Yang

Lian

et al. 2023

Front. Mol. Neurosci.

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“…According to our data, 24 h after MPTP administration, the expression of the Snca gene, which encodes another synaptic protein-α-synuclein-decreased. It is known that mutations in the α-synuclein gene lead to the development of PD, and its accumulation in Lewy bodies is a key element in the pathogenesis of the disease [79][80][81][82][83]. Considering that changes in Snca gene expression occur later than in the genes of other synaptic proteins we studied, the function of α-synuclein is not limited to the regulation of the pool of synaptic vesicles and their transport [84].…”

Section: Discussionmentioning

confidence: 99%

Initial Molecular Mechanisms of the Pathogenesis of Parkinson’s Disease in a Mouse Neurotoxic Model of the Earliest Preclinical Stage of This Disease

Kolacheva,

Pavlova,

Bannikova

et al. 2024

IJMS

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Studying the initial molecular mechanisms of the pathogenesis of Parkinson’s disease (PD), primarily in the nigrostriatal dopaminergic system, is one of the priorities in neurology. Of particular interest is elucidating these mechanisms in the preclinical stage of PD, which lasts decades before diagnosis and is therefore not available for study in patients. Therefore, our main goal was to study the initial molecular mechanisms of the pathogenesis of PD in the striatum, the key center for dopamine regulation in motor function, in a mouse model of the earliest preclinical stage of PD, from 1 to 24 h after the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). It was shown that the content of tyrosine hydroxylase (TH), the first enzyme in dopamine synthesis, does not change within 6 h after the administration of MPTP, but decreases after 24 h. In turn, TH activity increases after 1 h, decreases after 3 h, remains at the control level after 6 h, and decreases 24 h after the administration of MPTP. The concentration of dopamine in the striatum gradually decreases after MPTP administration, despite a decrease in its degradation. The identified initial molecular mechanisms of PD pathogenesis are considered as potential targets for the development of preventive neuroprotective treatment.

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Analysis of Behavior and Brain Neuronal Density in B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J Mice, a Parkinson’s Disease Model

Rozhkova,

Okotrub,

Brusentsev

et al. 2023

J Evol Biochem Phys

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The increase of α-synuclein and alterations of dynein in A53T transgenic and aging mouse

Cited by 6 publications

References 52 publications

Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Common mechanisms underlying axonal transport deficits in neurodegenerative diseases: a mini review

Initial Molecular Mechanisms of the Pathogenesis of Parkinson’s Disease in a Mouse Neurotoxic Model of the Earliest Preclinical Stage of This Disease

Analysis of Behavior and Brain Neuronal Density in B6.Cg-Tg(Prnp-SNCA*A53T)23Mkle/J Mice, a Parkinson’s Disease Model

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