دورية أكاديمية
Structural Features and Toxicity of α-Synuclein Oligomers Grown in the Presence of DOPAC
| العنوان: | Structural Features and Toxicity of α-Synuclein Oligomers Grown in the Presence of DOPAC |
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| المؤلفون: | Luana Palazzi, Benedetta Fongaro, Manuela Leri, Laura Acquasaliente, Massimo Stefani, Monica Bucciantini, Patrizia Polverino de Laureto |
| المصدر: | International Journal of Molecular Sciences, Vol 22, Iss 11, p 6008 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | α-synuclein aggregation inhibition, fibril inhibition, DOPAC, Parkinson’s disease, protein oligomerization, oligomer toxicity, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | The interplay between α-synuclein and dopamine derivatives is associated with oxidative stress-dependent neurodegeneration in Parkinson’s disease (PD). The formation in the dopaminergic neurons of intraneuronal inclusions containing aggregates of α-synuclein is a typical hallmark of PD. Even though the biochemical events underlying the aberrant aggregation of α-synuclein are not completely understood, strong evidence correlates this process with the levels of dopamine metabolites. In vitro, 3,4-dihydroxyphenylacetaldehyde (DOPAL) and the other two metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylethanol (DOPET), share the property to inhibit the growth of mature amyloid fibrils of α-synuclein. Although this effect occurs with the formation of differently toxic products, the molecular basis of this inhibition is still unclear. Here, we provide information on the effect of DOPAC on the aggregation properties of α-synuclein and its ability to interact with membranes. DOPAC inhibits α-synuclein aggregation, stabilizing monomer and inducing the formation of dimers and trimers. DOPAC-induced oligomers did not undergo conformational transition in the presence of membranes, and penetrated the cell, where they triggered autophagic processes. Cellular assays showed that DOPAC reduced cytotoxicity and ROS production induced by α-synuclein aggregates. Our findings show that the early radicals resulting from DOPAC autoxidation produced covalent modifications of the protein, which were not by themselves a primary cause of either fibrillation or membrane binding inhibition. These findings are discussed in the light of the potential mechanism of DOPAC protection against the toxicity of α-synuclein aggregates to better understand protein and catecholamine biology and to eventually suggest a scaffold that can help in the design of candidate molecules able to interfere in α-synuclein aggregation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/22/11/6008; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms22116008 |
| URL الوصول: | https://doaj.org/article/580295d8d3ec4f0eb5ca5f0431bfb25d |
| رقم الأكسشن: | edsdoj.580295d8d3ec4f0eb5ca5f0431bfb25d |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 14220067 16616596 |
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| DOI: | 10.3390/ijms22116008 |