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Microalgae Octapeptide IIAVEAGC Alleviates Oxidative Stress and Neurotoxicity in 6-OHDA-Induced SH-SY5Y Cells by
Yi Liu1, Liyuan Lin1, Haiyan Zheng1
1School of Chemistry and Environment, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, 524088, China.
Abstract:
Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti-oxidative stress activity. In this study, the stability of α-synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α-synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6-ohdainduced Parkinson's disease (PD) model SH-SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO-1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl-2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α-synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the prevention and treatment of neurodegenerative diseases.
Insights
This study shows that the microalgal peptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC) can protect neurons from oxidative stress and neurotoxicity. IEC demonstrates potential for preventing and treating neurodegenerative diseases like Parkinson's disease.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Neurodegenerative diseases involve neuronal loss due to factors like neurotoxicity and oxidative stress.
- Alpha-synuclein protein aggregation is a hallmark of some neurodegenerative conditions.
- Microalgae-derived peptides show potential for therapeutic applications.
Purpose of the Study:
- To investigate the neuroprotective effects of the microalgal octapeptide Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC).
- To evaluate IEC's efficacy against oxidative stress and neurotoxicity in a Parkinson's disease model.
- To elucidate the molecular mechanisms underlying IEC's neuroprotective actions.
Main Methods:
- Molecular dynamics simulations to assess alpha-synuclein binding stability with IEC.
- In vitro study using 6-hydroxydopamine (6-OHDA) induced Parkinson's disease model SH-SY5Y cells.
- Analysis of antioxidant enzyme expression (HO-1, GPX), apoptosis markers (Bcl-2/Bax ratio, caspase cascade), and signaling pathways (Nrf2, p53, Jak2/Stat3).
- Molecular docking to predict interactions between IEC and target proteins.
Main Results:
- IEC binding to alpha-synuclein was stabilized within 60 ns.
- IEC treatment increased antioxidant enzyme expression (HO-1, GPX) via the Nrf2 pathway.
- IEC protected cells by modulating apoptosis, increasing the Bcl-2/Bax ratio, inhibiting caspases, and affecting p53 and Jak2/Stat3 pathways.
- IEC demonstrated neuroprotective effects by inhibiting alpha-synuclein aggregation and reducing oxidative stress.
Conclusions:
- The microalgal peptide IEC exhibits significant neuroprotective properties against oxidative stress and neurotoxicity.
- IEC's mechanism involves enhancing antioxidant defenses and regulating apoptotic pathways.
- IEC shows promise as a therapeutic agent for neurodegenerative diseases, including Parkinson's disease.
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