Evidence map›Paper›PMID 37477766›Full record

ArticleMolecular neurobiology2023

Genome-wide CRISPR-Cas9 Knockout Screening Reveals a TSPAN3-mediated Endo-lysosome Pathway Regulating the Degradation of α-Synuclein Oligomers.

JunJian Hu, Xinjie Guan, Miao Zhao, Pengqing Xie, Jifeng Guo, Jieqiong Tan

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Article in Molecular neurobiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.6field-weighted citation impact, top 30% of its field
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

4 citing papers in PubMed, 3 citations in OpenAlex.

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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

6 authors at 1 institution in 2 countries.

JunJian HuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Xinjie GuanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Miao ZhaoCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Pengqing XieCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China.
Jifeng GuoDepartment of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
Jieqiong TanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Science, Central South University, Changsha, 410078, Hunan, China. tanjieqiong@sklmg.edu.cn.ORCID http://orcid.org/0000-0003-0730-1095
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Misfolding and aggregation of α-Synuclein (α-Syn), which are hallmark pathological features of neurodegenerative diseases such as Parkinson's disease (PD) and dementia with Lewy Bodies, continue to be significant areas of research. Among the diverse forms of α-Syn - monomer, oligomer, and fibril, the oligomer is considered the most toxic. However, the mechanisms governing α-Syn oligomerization are not yet fully understood. In this study, we utilized genome-wide CRISPR/Cas9 loss-of-function screening in human HEK293 cells to identify negative regulators of α-Syn oligomerization. We found that tetraspanin 3 (TSPAN3), a presumptive four-pass transmembrane protein, but not its homolog TSPAN7, significantly modulates α-Syn oligomer levels. TSPAN3 was observed to interact with α-Syn oligomers, regulate the amount of α-Syn oligomers on the cell membrane, and promote their degradation via the clathrin-AP2 mediated endo-lysosome pathway. Our findings highlight TSPAN3 as a potential regulator of α-Syn oligomers, presenting a promising target for future PD prevention and treatment strategies.

Indexed as

alpha-SynucleinCRISPR-Cas SystemsEndosomesGene Knockout TechniquesLysosomesProtein MultimerizationProteolysisTetraspaninsHEK293 CellsHumansalpha-SynucleinTetraspaninsCRISPR-Cas9DegradationLysosomeTSPAN3α-Synuclein

Identifiers

PMID37477766
OpenAlexW4384922859

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.