Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson's disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD.

Authors

Institutions

Publication Details

Journal
Cell Communication and Signaling
Published
2025-02-03
DOI
https://doi.org/10.1186/s12964-025-02037-x
Citations
3
Primary Topic
Parkinson's Disease Mechanisms and Treatments
Type
article
Field-Weighted Citation Impact
4.17

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice

Xinjiang Kang, Anqi Wei, Bianbian Wang, Jingyu Yao et al.
3 citations
Cell Communication and Signaling
Parkinson's Disease Mechanisms and Treatments
4.17
article

Compensatory synaptotagmin-11 expression conceals parkinson’s disease-like phenotypes in parkin knockout mice

Xinjiang Kang, Anqi Wei, Bianbian Wang, Jingyu Yao, Chaowen Zheng, Changhe Wang, Nan Dong, Yuhao Gu, Zhenli Xie, Yongning Deng, Guoqing Chen, Yuqing Zhang, Xi Zhang, Qiumin Qu, Yuxin Yang, Xu Cheng, Yuhao Qin, Yang Chen, Hua Xu
article en
3 citations

Abstract

Animal models are crucial for elucidating the pathological mechanisms underlying Parkinson's disease (PD). Unfortunately, most of transgenic mouse models fail to manifest pathological changes observed in PD patients, pending the advancement of PD research. However, the mechanism underlying this discrepancy remains elusive. Here, we provide compelling evidence that the compensatory expression of synaptotagmin-11 (Syt11) plays a key role in concealing PD-associated phenotypes in parkin knockout (KO) mouse models. Unlike the normal dopamine (DA) release and motor behaviors observed in parkin KO mice, parkin knockdown (KD) in the substantia nigra pars compacta (SNpc) in adult mice led to both the impaired DA release and the pronounced motor deficits. Interestingly, Syt11, a well-established parkin substrate involved in PD, was specifically upregulated in parkin KD mice and in parkin KO mice during the suckling stage, but not in adult parkin KO mice. Importantly, the overexpression of Syt11 alone is capable of inducing PD-like motor and non-motor impairments, as well as the impaired DA release and reuptake, which is essential for parkin-associated pathogenesis of PD. Therefore, this work not only elucidate a compensatory mechanism that accounts for the absence of overt PD phenotypes in parkin KO mice, but also contribute to the comprehensive understanding of the progression of PD, opening new avenues for the therapeutic treatment of PD.

Cell Communication and SignalingVol. 23(1)
Capital Medical University (CN), Liaocheng University (CN), Peking University (CN), Southwest Medical University (CN), Ministry of Education (IR), Chinese Institute for Brain Research (CN), First Affiliated Hospital of Xi'an Jiaotong University (CN), Second Affiliated Hospital of Xi'an Jiaotong University (CN), Center for Life Sciences (CN), Xi'an Jiaotong University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, Natural Science Foundation of Shaanxi Province, Directorate for Biological Sciences
Zero hunger
Openalex Percentile: Top 8%
Parkinson's Disease Mechanisms and Treatments
4.17
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.