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Cited by 44Parkinson's Disease Mechanisms and TreatmentsCellular transport and secretionNeuroscience and Neuropharmacology Research

Dysfunction of Synaptic Vesicle Endocytosis in Parkinson’s Disease

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Zou, Li, Tian, Ye, Zhang, Zhentao·2021·Frontiers in Integrative Neuroscience
DOI 10.3389/fnint.2021.619160PMC PMC8172812
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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease. It is a chronic and progressive disorder estimated to affect at least 4 million people worldwide. Although the etiology of PD remains unclear, it has been found that the dysfunction of synaptic vesicle endocytosis (SVE) in neural terminal happens before the loss of dopaminergic neurons. Recently, accumulating evidence reveals that the PD-linked synaptic genes, including DNAJC6, SYNJ1, and SH3GL2, significantly contribute to the disruptions of SVE, which is vital for the pathogenesis of PD. In addition, the proteins encoded by other PD-associated genes such as SNCA, LRRK2, PRKN, and DJ-1 also play key roles in the regulation of SVE. Here we present the facts about SVE-related genes and discussed their potential relevance to the pathogenesis of PD.

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Crossref · 10.3389/fnint.2021.619160

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  • Recycling of synaptic vesicles comprises three key steps at the synapse: release of neurotransmitters, clathrin-mediated endocytosis, and ultrafast endocytosis.

    “The recycling of synaptic vesicles is the hallmark event which comprises three key steps at the synapse; (i) release of neurotransmitters, (ii) clathrin-mediated endocytosis, and (iii) ultrafast endocytosis [149].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [149]

    The Synaptic Vesicle Recycling section describes neurotransmitter release, clathrin-mediated endocytosis, and ultrafast endocytosis. But it lists additional steps in vesicle activity and describes the two forms of endocytosis as alternative pathways, not as two successive steps in a three-step sequence. No page number is available in our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Synaptic vesicle endocytosis dysfunction leads to erroneous dopamine packaging into vesicles, as a consequence of elevated cytosolic dopamine and subsequent dopaminergic neurodegeneration.

    “The SVE dysfunction leads to erroneous dopamine packaging into the vesicles, as a consequence of elevated cytosolic dopamine and subsequent dopaminergic neurodegeneration [149].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [149]

    The ‘Axon Degeneration and SVE Dysfunction in PD’ section proposes that SVE dysfunction may cause incorrect dopamine packaging, leading to increased cytosolic dopamine and ultimately contributing to dopaminergic neurodegeneration (page not available). The citing sentence presents this proposed pathway as definite; its wording also appears to place elevated cytosolic dopamine before, rather than after, incorrect packaging. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Numerous proteins including AMPH1, endophilin A1, clathrin, dynamin, and SYNJ1 play vital roles in mechanisms of endocytosis.

    “Numerous proteins play vital roles in the mechanisms of endocytosis, including amphiphysin 1 (AMPH1), endophilin A1, clathrin, dynamin, and synaptojanin 1 (SYNJ1) [149].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [149]

  • Genes DNAJC6, SYNJ1, SH3GL2, SNCA, LRRK2, PRKN, and DJ-1 play a vital role in modulation of synaptic vesicle endocytosis and progression of Parkinson's disease.

    “Several genetic studies and mutation analysis suggest that the genes such as DNAJC6, SYNJ1, SH3GL2, SNCA, LRRK2, PRKN, and DJ-1 plays a vital role in the modulation of SVE and progression of PD [149].”

    From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [149]

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Cited by

Sorted by citations

Authors
Zou, L., Tian, Y., & Zhang, Z.
Affiliations
Renmin Hospital of Wuhan University (CN)
Corresponding author
Zhang, Zhentao
ORCID
Venue
Frontiers in Integrative Neuroscience
Publisher
Frontiers Media SA
Published
2021-05-20
Volume
15
Pages
619160-619160
ISSN
1662-5145 (ISSN-L)
DOI
10.3389/fnint.2021.619160
PMC
PMC8172812
OpenAlex
W3165269763
Cited by
44
References
8
Citations by year
2026: 12 · 2025: 8 · 2024: 8 · 2023: 10 · 2022: 6
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Integrative Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81822016, 81771382, 81571249)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Parkinson's disease, synaptic vesicle endocytosis, dopaminergic neurons, DNAJC6, SYNJ1, SH3GL2, SNCA, LRRK2, Parkin, DJ-1, synaptic genes, neurodegeneration, presynaptic terminals

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