A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death
<b>Background/Objectives:</b> Parkinson’s disease (PD) is a neuro-degenerative disease for which a radical cure is not available, only symptomatic control. Studies have shown that hypoxia may have disease-modifying effects on PD. <b>Methods:</b> Herein, we investigated whethe...
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2025-03-01
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| author | Ha Nyeoung Choi Seon-Hee Kim Min Gi Jo Bina Lee Young Jin Kim So Eun Lee Jeong Hyun Lee Hye Min Seong Seong Jae Kim Sang Won Park Hye Jung Kim Heeyoung Kang Chan Hyun Lee Min Young Lee Seung Pil Yun Minkyeong Kim |
| author_facet | Ha Nyeoung Choi Seon-Hee Kim Min Gi Jo Bina Lee Young Jin Kim So Eun Lee Jeong Hyun Lee Hye Min Seong Seong Jae Kim Sang Won Park Hye Jung Kim Heeyoung Kang Chan Hyun Lee Min Young Lee Seung Pil Yun Minkyeong Kim |
| author_sort | Ha Nyeoung Choi |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> Parkinson’s disease (PD) is a neuro-degenerative disease for which a radical cure is not available, only symptomatic control. Studies have shown that hypoxia may have disease-modifying effects on PD. <b>Methods:</b> Herein, we investigated whether short-term hypoxia activates astrocytes and whether it has a protective effect on pre-formed fibril (PFF)-treated primary cortical neurons. <b>Results:</b> Long-term hypoxia suppresses astrocyte activation and induces cell death, whereas short-term hypoxia activates astrocytes without affecting cellular apoptosis or viability. Short-term hypoxia restored the cellular apoptosis and viability of PFF-treated neurons and reduced toxic phospho-α-synuclein (p-α-syn) aggregation. Similarly, the short-term hypoxia-exposed astrocyte-conditioned medium rescued cellular apoptosis and the viability of PFF-treated neurons and p-α-syn expression. Quantitative polymerase chain reaction revealed that short-term hypoxia promotes protective A2 astrocytes and suppresses toxic A1 astrocytes. <b>Conclusions</b>: Our findings suggest that short-term hypoxia has a neuro-protective effect against PD by activating protective A2 astrocytes, which rescue PFF-induced neuronal cell death. This provides insights into the clinical implications of short-term hypoxia as a disease-modifying PD strategy. |
| format | Article |
| id | doaj-art-7099839c883d4853bbdf609200b60e55 |
| institution | DOAJ |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-7099839c883d4853bbdf609200b60e552025-08-20T02:42:35ZengMDPI AGBiomedicines2227-90592025-03-0113360410.3390/biomedicines13030604A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell DeathHa Nyeoung Choi0Seon-Hee Kim1Min Gi Jo2Bina Lee3Young Jin Kim4So Eun Lee5Jeong Hyun Lee6Hye Min Seong7Seong Jae Kim8Sang Won Park9Hye Jung Kim10Heeyoung Kang11Chan Hyun Lee12Min Young Lee13Seung Pil Yun14Minkyeong Kim15Department of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pathology, College of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Ophthalmology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of KoreaDepartment of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of KoreaCollege of Pharmacy, Research Institute of Pharmaceutical Sciences, Vessel-Organ Interaction Research Center (VOICE, MRC), Kyungpook National University, Daegu 41566, Republic of KoreaDepartment of Pharmacology, Institute of Medical Science, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of KoreaDepartment of Neurology, Gyeongsang National University Hospital, Jinju 52727, Republic of Korea<b>Background/Objectives:</b> Parkinson’s disease (PD) is a neuro-degenerative disease for which a radical cure is not available, only symptomatic control. Studies have shown that hypoxia may have disease-modifying effects on PD. <b>Methods:</b> Herein, we investigated whether short-term hypoxia activates astrocytes and whether it has a protective effect on pre-formed fibril (PFF)-treated primary cortical neurons. <b>Results:</b> Long-term hypoxia suppresses astrocyte activation and induces cell death, whereas short-term hypoxia activates astrocytes without affecting cellular apoptosis or viability. Short-term hypoxia restored the cellular apoptosis and viability of PFF-treated neurons and reduced toxic phospho-α-synuclein (p-α-syn) aggregation. Similarly, the short-term hypoxia-exposed astrocyte-conditioned medium rescued cellular apoptosis and the viability of PFF-treated neurons and p-α-syn expression. Quantitative polymerase chain reaction revealed that short-term hypoxia promotes protective A2 astrocytes and suppresses toxic A1 astrocytes. <b>Conclusions</b>: Our findings suggest that short-term hypoxia has a neuro-protective effect against PD by activating protective A2 astrocytes, which rescue PFF-induced neuronal cell death. This provides insights into the clinical implications of short-term hypoxia as a disease-modifying PD strategy.https://www.mdpi.com/2227-9059/13/3/604Parkinson’s disease (PD)hypoxiaastrocyteneuronal deathpre-formed fibril |
| spellingShingle | Ha Nyeoung Choi Seon-Hee Kim Min Gi Jo Bina Lee Young Jin Kim So Eun Lee Jeong Hyun Lee Hye Min Seong Seong Jae Kim Sang Won Park Hye Jung Kim Heeyoung Kang Chan Hyun Lee Min Young Lee Seung Pil Yun Minkyeong Kim A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death Biomedicines Parkinson’s disease (PD) hypoxia astrocyte neuronal death pre-formed fibril |
| title | A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death |
| title_full | A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death |
| title_fullStr | A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death |
| title_full_unstemmed | A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death |
| title_short | A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death |
| title_sort | a2 astrocyte activation by short term hypoxia rescues α synuclein pre formed fibril induced neuronal cell death |
| topic | Parkinson’s disease (PD) hypoxia astrocyte neuronal death pre-formed fibril |
| url | https://www.mdpi.com/2227-9059/13/3/604 |
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