Evidence map›Paper›PMID 41186735›Full record

ArticleHuman genetics2025

Deficiency of SCAMP5 causes Parkinson's disease due to loss of dopamine neurons.

Huihui Liu, Shunnan Ge, Zhenxing Liu, Meiqi Hou, Weimin Jia, Jinze Li, Guihua Wang, Nianyi Sun, Xuelian Wang, Xianqin Zhang

Abstract read
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In one paragraph

Article in Human genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Huihui Liu *Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Shunnan Ge *Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Zhenxing LiuKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Meiqi HouKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Weimin JiaKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Jinze LiKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Guihua WangKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Nianyi SunKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China.
Xuelian WangDepartment of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, China.
Xianqin ZhangKey Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, China. xqzhang04@hust.edu.cn.

Funding

National Key R&D Program of China 2023YFC2706302National Natural Science Foundation of China 81000079, 81170165, and 81870959Program for HUST Academic Frontier Youth Team 2016QYTD02
6 · The paper itself

Abstract

Parkinson's disease is a progressive neurodegenerative disorder characterized by symptoms such as bradykinesia, resting tremors, and muscle rigidity. Although several disease-causing genes of juvenile Parkinson's disease have been reported, the underlying mechanism remains unclear. Here, we identified SCAMP5 as a novel disease-causing gene of Parkinson's disease in a consanguineous family with juvenile Parkinson's disease. Functional studies in PC12 cell lines revealed that SCAMP5 deficiency increased the level of α-synuclein protein and α-synuclein oligomers, leading to increased cell apoptosis and decreased dopamine secretion. SCAMP5 knockdown in SH-SY5Y cells reduces α-synuclein secretion via exosome. Expression of human wild-type SCAMP5 rescued these effects, whereas the R91W mutant SCAMP5 did not. Scamp5a knockout zebrafish showed Parkinson's disease-like phenotypes, including bradykinesia, loss of dopamine neurons and decreased dopamine content in the brain. Transcriptome analysis unveiled upregulated JNK signaling in scamp5a knockout zebrafish, contributing to neuronal apoptosis. Importantly, human SCAMP5 prevented both dopamine neuron loss and bradykinesia in scamp5a knockout zebrafish, suggesting its therapeutic potential in Parkinson's disease. Overall, our findings identify SCAMP5 as a novel disease-causing gene of Parkinson's disease and highlight its neuroprotective role, opening new avenues for Parkinson's disease treatment.

Indexed as

Dopaminergic NeuronsMembrane ProteinsParkinson Diseasealpha-SynucleinAnimalsApoptosisDopamineFemaleHumansMalePC12 CellsPedigreeRatsZebrafishalpha-SynucleinDopamineMembrane Proteins

Identifiers

PMID41186735

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.