Evidence mapPaperPMID 41258150Full record

ArticleNPJ Parkinson's disease2025

A novel peptide-based strategy to enhance GBA1 expression for treating Parkinson's disease.

Hyerynn Kim, Jiyeon Na, Hye Guk Ryu, Eunmin Lee, Hyeonwoo Park, Haeun Park, Younwoo Nam, Geon-Hwi Jeong, In-Hyeok Pyo, Jung-Hyun Choi and 5 more

Abstract read
In one paragraph

Article in NPJ Parkinson's disease, 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

15 authors.

Hyerynn KimDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jiyeon NaDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Hye Guk RyuDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Eunmin LeeDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Hyeonwoo ParkDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Haeun ParkDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Younwoo NamDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Geon-Hwi JeongDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
In-Hyeok PyoDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jung-Hyun ChoiDepartment of Biochemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jihoon NahDepartment of Biochemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Sang-Min JangDepartment of Biochemistry, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jun-Ho SongDepartment of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Sung-Jin Cho *Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. sjchobio@chungbuk.ac.kr.
Sangjune Kim *Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. sangjune@chungbuk.ac.kr.

Funding

National Research Foundation of Korea RS-2022-NR072007National Research Foundation of Korea RS-2024-00445180
6 · The paper itself

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by α-synuclein aggregation and lysosomal dysfunction, with GBA1 mutations representing the most common genetic risk factor. Reduced glucocerebrosidase (GCase) activity is observed in both familial and sporadic PD, promoting α-synuclein accumulation and neuronal toxicity. Here, we developed a GBA1-HiBiT tagged knock-in HEK293T reporter system, providing a highly sensitive, real-time quantitative measurement of GCase dynamics. From a leech-derived peptide library, we identified a cell-penetrating peptide hirunipin 4 that significantly enhanced GCase protein levels and enzymatic activity. Moreover, hirunipin 4 alleviated α-synuclein preformed fibrils (PFF)-induced lysosomal dysfunction and glucosylceramide accumulation. Thus, hirunipin 4 was able to reduce PFF-induced pathological α-synuclein accumulation and neurotoxicity in both SH-SY5Y and primary cortical neurons. Mechanistically, hirunipin 4 promoted nuclear translocation of TFEB and enhanced GCase protein stability. These findings highlight the utility of the GBA1-HiBiT platform for peptide-based screening and identify hirunipin 4 as a promising candidate for restoring lysosomal function in PD.

Identifiers

PMID41258150
PMCPMC12630718

What Socratic holds

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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.