Scholarlink

<p>In the current study, the effects of N-homocysteine thiolactone (HcyT) modification on expressed α-synuclein and the SH-SY5Y cell line were investigated. Various fluorometric, cell viability, and flow cytometry assays were employed to analyze the extent and impacts of modification under reducing/non-reducing conditions and different incubation durations. Our results confirmed that under non-reducing conditions, protofibrils exhibited a heightened propensity for aggregation with longer incubation periods. The increased tendency for aggregates following modification could be attributed to intermolecular forces, notably the establishment of π-stacking and hydrophobic interactions, consequent to the disruption of electrostatic charges due to lysine residues. Furthermore, our findings corroborated that N-homocysteinylation of α-synuclein by HcyT induces apoptosis in SH-SY5Y cells, suggesting that such a modification may indeed contribute to the onset and progression of Parkinson’s disease (PD) in patients. Deciphering the underlying mechanisms using enhanced resolution techniques at the molecular level can pave the way to unraveling the pathogenesis associated with PD, as well as proposing effective strategies and countermeasures to mitigate the onset and progression of the disease. In light of the discoveries reported herein, N-homocysteinylation can be considered a risk factor and a potential biomarker in structural diseases, such as neurodegenerative disorders. Additionally, we propose that inhibiting N-homocysteinylation may impede protein aggregates and prevent the progression of neurodegeneration associated with these aggregates.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

N-Homocysteinylation of lysine residues in α-Synuclein enhances aggregation propensity and cytotoxicity in SH-SY5Y cells

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

查看全文
  • Mohsen Masoumian Hosseini,
  • Manhal Abdulameer,
  • Roya Altafi,
  • Dina Morshedi,
  • Ali Es-haghi,
  • Seyyed Hossein Khatami,
  • Farzaneh Salmani,
  • Hessam Sepasi Tehrani,
  • Sajad Ehtiati,
  • Marziyeh Goudarzi,
  • Bahram Gholamali Yaghmaei,
  • Saeed Karima

摘要

In the current study, the effects of N-homocysteine thiolactone (HcyT) modification on expressed α-synuclein and the SH-SY5Y cell line were investigated. Various fluorometric, cell viability, and flow cytometry assays were employed to analyze the extent and impacts of modification under reducing/non-reducing conditions and different incubation durations. Our results confirmed that under non-reducing conditions, protofibrils exhibited a heightened propensity for aggregation with longer incubation periods. The increased tendency for aggregates following modification could be attributed to intermolecular forces, notably the establishment of π-stacking and hydrophobic interactions, consequent to the disruption of electrostatic charges due to lysine residues. Furthermore, our findings corroborated that N-homocysteinylation of α-synuclein by HcyT induces apoptosis in SH-SY5Y cells, suggesting that such a modification may indeed contribute to the onset and progression of Parkinson’s disease (PD) in patients. Deciphering the underlying mechanisms using enhanced resolution techniques at the molecular level can pave the way to unraveling the pathogenesis associated with PD, as well as proposing effective strategies and countermeasures to mitigate the onset and progression of the disease. In light of the discoveries reported herein, N-homocysteinylation can be considered a risk factor and a potential biomarker in structural diseases, such as neurodegenerative disorders. Additionally, we propose that inhibiting N-homocysteinylation may impede protein aggregates and prevent the progression of neurodegeneration associated with these aggregates.