Scholarlink

<p>Parkinson’s disease (PD), characterized by α-Synuclein aggregation and dopaminergic neuronal loss, has no current cure. Autophagy is critical for α-Synuclein clearance, yet its real-time dynamics remain challenging to assess in human-relevant systems. Here, we used live-cell imaging to assess autophagy within human neuronal cultures and midbrain organoids (hMOs) derived from induced pluripotent stem cells (iPSCs) of PD patients carrying a triplication of the α-Synuclein gene (3xSNCA). Using the LC3-Rosella dual-fluorescent reporter, we quantified autolysosomes dynamics in real time. In 3xSNCA neuronal cultures, we detected early autophagy defects. In 3xSNCA hMOs, reduced autolysosome area, increased total and phosphorylated α-Synuclein (pS129), and decreased electrophysiological activity were observed at 50 days of differentiation (DoD). By 70 DoD, autophagy impairment became more pronounced, overlapping with dopaminergic neuron dysfunction. These findings support the use of human iPSCs-derived models to study autophagy dysfunction in PD and demonstrate a temporal correlation between impaired autophagy, α-Synuclein pathology and neuronal degeneration.</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

Autophagy dysfunction in iPSCs-derived neurons and midbrain organoids carrying a SNCA triplication

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月31日

查看全文
  • Catarina Serra-Almeida,
  • Javier Jarazo,
  • Gemma Gomez-Giro,
  • Isabel Rosety,
  • Alise Zagare,
  • Daniele Ferrante,
  • Cláudia Saraiva,
  • Daniela Frangenberg,
  • Jennifer Modamio-Chamarro,
  • Elisa Zuccoli,
  • Ana Clara Cristóvão,
  • Liliana Bernardino,
  • Jens Christian Schwamborn

摘要

Parkinson’s disease (PD), characterized by α-Synuclein aggregation and dopaminergic neuronal loss, has no current cure. Autophagy is critical for α-Synuclein clearance, yet its real-time dynamics remain challenging to assess in human-relevant systems. Here, we used live-cell imaging to assess autophagy within human neuronal cultures and midbrain organoids (hMOs) derived from induced pluripotent stem cells (iPSCs) of PD patients carrying a triplication of the α-Synuclein gene (3xSNCA). Using the LC3-Rosella dual-fluorescent reporter, we quantified autolysosomes dynamics in real time. In 3xSNCA neuronal cultures, we detected early autophagy defects. In 3xSNCA hMOs, reduced autolysosome area, increased total and phosphorylated α-Synuclein (pS129), and decreased electrophysiological activity were observed at 50 days of differentiation (DoD). By 70 DoD, autophagy impairment became more pronounced, overlapping with dopaminergic neuron dysfunction. These findings support the use of human iPSCs-derived models to study autophagy dysfunction in PD and demonstrate a temporal correlation between impaired autophagy, α-Synuclein pathology and neuronal degeneration.