Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease
Abstract The application of extracellular vesicles (EVs) as vehicles for anti‐Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood‐brain barrier (BBB) targeting strategies. In this study, we e...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | Journal of Extracellular Vesicles |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jev2.70018 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841525461055700992 |
|---|---|
| author | Jae Hoon Sul Sol Shin Hark Kyun Kim Jihoon Han Junsik Kim Soyoung Son Jungmi Lee Seung Hyun Baek Yoonsuk Cho Jeongmi Lee Jinsu Park Donghoon Ahn Sunyoung Park Leon F. Palomera Jeein Lim Jongho Kim Chanhee Kim Seungsu Han Ka Young Chung Sangho Lee Tae‐in Kam Yunjong Lee Jeongyun Kim Jae Hyung Park Dong‐Gyu Jo |
| author_facet | Jae Hoon Sul Sol Shin Hark Kyun Kim Jihoon Han Junsik Kim Soyoung Son Jungmi Lee Seung Hyun Baek Yoonsuk Cho Jeongmi Lee Jinsu Park Donghoon Ahn Sunyoung Park Leon F. Palomera Jeein Lim Jongho Kim Chanhee Kim Seungsu Han Ka Young Chung Sangho Lee Tae‐in Kam Yunjong Lee Jeongyun Kim Jae Hyung Park Dong‐Gyu Jo |
| author_sort | Jae Hoon Sul |
| collection | DOAJ |
| description | Abstract The application of extracellular vesicles (EVs) as vehicles for anti‐Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood‐brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose‐derived stem cell EVs (Dopa‐EVs) utilizing a facile, two‐step cross‐linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa‐EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa‐EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6‐hydroxydopamine (6‐OHDA) and α‐Syn PFF‐induced PD models. Furthermore, we observed that Dopa‐EVs stimulated autophagy evidenced by the upregulation of Beclin‐1 and LC3‐II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa‐EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities. |
| format | Article |
| id | doaj-art-70f36632e2e34240a23f22571dabc1c8 |
| institution | Kabale University |
| issn | 2001-3078 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Extracellular Vesicles |
| spelling | doaj-art-70f36632e2e34240a23f22571dabc1c82025-01-17T11:11:12ZengWileyJournal of Extracellular Vesicles2001-30782024-12-011312n/an/a10.1002/jev2.70018Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's diseaseJae Hoon Sul0Sol Shin1Hark Kyun Kim2Jihoon Han3Junsik Kim4Soyoung Son5Jungmi Lee6Seung Hyun Baek7Yoonsuk Cho8Jeongmi Lee9Jinsu Park10Donghoon Ahn11Sunyoung Park12Leon F. Palomera13Jeein Lim14Jongho Kim15Chanhee Kim16Seungsu Han17Ka Young Chung18Sangho Lee19Tae‐in Kam20Yunjong Lee21Jeongyun Kim22Jae Hyung Park23Dong‐Gyu Jo24School of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of Chemical Engineering, College of EngineeringSungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of Chemical Engineering, College of EngineeringSungkyunkwan UniversitySuwonRepublic of KoreaSchool of Chemical Engineering, College of EngineeringSungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaDepartment of Health Sciences and TechnologySAIHST, Sungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaDepartment of Biological SciencesSungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaDepartment of Biological SciencesSungkyunkwan UniversitySuwonRepublic of KoreaDepartment of Brain and Cognitive SciencesKorea Advanced Institute of Science and TechnologyDaejeonRepublic of KoreaDepartment of Molecular Cell BiologySungkyunkwan University School of MedicineSuwon Republic of KoreaDepartment of Health Sciences and TechnologySAIHST, Sungkyunkwan UniversitySuwonRepublic of KoreaSchool of Chemical Engineering, College of EngineeringSungkyunkwan UniversitySuwonRepublic of KoreaSchool of PharmacySungkyunkwan UniversitySuwonRepublic of KoreaAbstract The application of extracellular vesicles (EVs) as vehicles for anti‐Parkinson's agents represents a significant advance, yet their clinical translation is hampered by challenges in efficient brain delivery and complex blood‐brain barrier (BBB) targeting strategies. In this study, we engineered dopamine onto the surface of adipose‐derived stem cell EVs (Dopa‐EVs) utilizing a facile, two‐step cross‐linking approach. This engineering enhanced neuronal uptake of the EVs in primary neurons and neuroblastoma cells, a process shown to be competitively inhibited by dopamine pretreatment and dopamine receptor antibodies. Notably, Dopa‐EVs demonstrated increased brain accumulation in mouse Parkinson's disease (PD) models. Therapeutically, Dopa‐EVs administration led to the rescue of dopaminergic neuronal loss and amelioration of behavioural deficits in both 6‐hydroxydopamine (6‐OHDA) and α‐Syn PFF‐induced PD models. Furthermore, we observed that Dopa‐EVs stimulated autophagy evidenced by the upregulation of Beclin‐1 and LC3‐II. These findings collectively indicate that surface modification of EVs with dopamine presents a potent strategy for targeting dopaminergic neurons in the brain. The remarkable therapeutic potential of Dopa‐EVs, demonstrated in PD models, positions them as a highly promising candidate for PD treatment, offering a significant advance over current therapeutic modalities.https://doi.org/10.1002/jev2.70018autophagydopamineexosomeextracellular vesiclesParkinson's disease |
| spellingShingle | Jae Hoon Sul Sol Shin Hark Kyun Kim Jihoon Han Junsik Kim Soyoung Son Jungmi Lee Seung Hyun Baek Yoonsuk Cho Jeongmi Lee Jinsu Park Donghoon Ahn Sunyoung Park Leon F. Palomera Jeein Lim Jongho Kim Chanhee Kim Seungsu Han Ka Young Chung Sangho Lee Tae‐in Kam Yunjong Lee Jeongyun Kim Jae Hyung Park Dong‐Gyu Jo Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease Journal of Extracellular Vesicles autophagy dopamine exosome extracellular vesicles Parkinson's disease |
| title | Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease |
| title_full | Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease |
| title_fullStr | Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease |
| title_full_unstemmed | Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease |
| title_short | Dopamine‐conjugated extracellular vesicles induce autophagy in Parkinson's disease |
| title_sort | dopamine conjugated extracellular vesicles induce autophagy in parkinson s disease |
| topic | autophagy dopamine exosome extracellular vesicles Parkinson's disease |
| url | https://doi.org/10.1002/jev2.70018 |
| work_keys_str_mv | AT jaehoonsul dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT solshin dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT harkkyunkim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jihoonhan dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT junsikkim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT soyoungson dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jungmilee dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT seunghyunbaek dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT yoonsukcho dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jeongmilee dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jinsupark dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT donghoonahn dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT sunyoungpark dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT leonfpalomera dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jeeinlim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jonghokim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT chanheekim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT seungsuhan dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT kayoungchung dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT sangholee dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT taeinkam dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT yunjonglee dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jeongyunkim dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT jaehyungpark dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease AT donggyujo dopamineconjugatedextracellularvesiclesinduceautophagyinparkinsonsdisease |