A2-Astrocyte Activation by Short-Term Hypoxia Rescues α-Synuclein Pre-Formed-Fibril-Induced Neuronal Cell Death

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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Biomedicines
Subjects:
Parkinson’s disease (PD)
hypoxia
astrocyte
neuronal death
pre-formed fibril
Online Access:https://www.mdpi.com/2227-9059/13/3/604
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Summary:<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.
ISSN:2227-9059

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