Visualizing Endoplasmic Reticulum Stress and Autophagy in Alzheimer's Model Cells by a Peroxynitrite-Responsive
Lushan Huang1,2, Liyi Ma1,2, Qichen Zhu1,2
1Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
ACS Chemical Neuroscience
|January 7, 2025
Summary
Researchers developed a new fluorescent probe to visualize endoplasmic reticulum (ER) stress and ER-phagy in Alzheimer's disease (AD) models. The probe tracks peroxynitrite, revealing its role in ER stress and ferroptosis, and highlights ER-phagy's potential protective function.
Area of Science:
- Neuroscience
- Biochemistry
- Cell Biology
Background:
- Endoplasmic reticulum (ER) stress and ER-autophagy (ER-phagy) are critical in Alzheimer's disease (AD) pathogenesis.
- Peroxynitrite (ONOO-) is a key mediator in ER stress and ER-phagy, influencing AD progression.
- Visualizing these processes is essential for understanding AD mechanisms.
Purpose of the Study:
- To design and synthesize an innovative ONOO--responsive, aggregation-induced emission (AIE) fluorescent probe (DHQM) for monitoring ER stress and ER-phagy in AD model cells.
- To investigate the role of ONOO- in ER stress and ferroptosis in aluminum-induced AD models.
- To explore the potential of ER-phagy in mitigating ER stress and ferroptosis.
Main Methods:
- Synthesis of an ONOO--responsive AIE fluorescent probe (DHQM).
- Characterization of DHQM's AIE properties, sensitivity, selectivity, and ER-targeting ability.
- Application of DHQM for fluorescence imaging of ER ONOO- fluctuations and ER stress in aluminum-induced AD model cells.
Main Results:
- DHQM exhibited excellent AIE properties, high sensitivity, selectivity for ONOO-, and ER-targeting capabilities for washing-free intracellular imaging.
- DHQM successfully visualized ER ONOO- fluctuations and ER stress in aluminum-induced AD model cells.
- Aluminum-induced ferroptosis was identified as a source of excessive ONOO-, exacerbating ER stress; ER-phagy was observed and may play a protective role.
Conclusions:
- The developed DHQM probe is effective for visualizing ER stress and ER-phagy, offering insights into AD pathology.
- Excessive ONOO- production, linked to ferroptosis, significantly contributes to ER stress in AD models.
- ER-phagy presents a potential therapeutic target for mitigating ER stress and ferroptosis in Alzheimer's disease.
