Stroke Drug Development Targeting Autophagy

Autophagy is a double-edged sword in the development of stroke pathology and can modulate the stroke process in different ways, but the exact mechanism of action is not yet clear. It is now generally accepted that moderate autophagy activation is neuroprotective, whereas excessive autophagy activation is detrimental. Therefore, a potential therapeutic avenue for stroke treatment is through rational and effective regulation of the autophagic process. With this in mind, Ace Therapeutics has established a complete and well-established workflow for the study of stroke drug development targeting autophagy.

High-Throughput Screening of Autophagy Modulators

In order to explore the important regulatory role of autophagy in stroke, we should screen a large number of autophagy modulators and then evaluate the role of autophagy modulators on the stroke process under different experimental conditions. Based on our ultra-large compound library, natural product library, and fragment library, we provide different screening platforms for autophagy modulators to meet your different needs.

• mRFP-GFP-LC3-based high-throughput cellular autophagy flux screening platform
  Based on cells stably expressing mRFP-GFP-LC3 to detect autophagic flux, we can provide more stable and reliable analysis results.
• GFP-LC3-RFP-LC3ΔG-based high-throughput cellular autophagy flux screening platform
  The readouts can be quantified by fluorescence microscopy, microplate reader, or flow cytometry.
• High-throughput cellular screening platform based on autophagic clearance of aggregation-prone proteins
  Screens for the role of autophagy on aggregation-prone proteins produced by stroke.

Preclinical Evaluation of Drug Candidates for the Treatment of Stroke

After screening to obtain a large number of autophagy modulators, we explore the effects of these autophagy modulators on stroke. Because differences in the type of stroke model, the type of autophagy modulator, the duration of action of the autophagy modulator, and the dose of autophagy modulator used can have a large or even opposite effect on the pathological outcome of stroke, Ace Therapeutics has established a complete service to explore the pharmacological activity of autophagy on stroke.

• Our stroke models cover all in vitro and in vivo model categories.
• We have excellent scientists who strictly control the conditions of modeling to ensure the scientific validity and reproducibility of the experiments.
• We set multiple doses of autophagy modulators in the range of non-toxic concentrations to investigate the effect of autophagy modulators on stroke at different concentrations.
• Since autophagy modulators regulate stroke pathological processes in a time-dependent manner, we add more time points to detect the effect of autophagy modulators on stroke at different times.
• We explore the effect of adding autophagy modulators at different times after stroke on the pathological process of stroke.

Ace Therapeutics has various testing platforms, such as observation of autophagosomes by transmission electron microscopy, tracing of autophagy formation by GFP-LC3 fusion protein, and expression of related genes or proteins by ELISA, western blotting, and qPCR assays, to verify the pharmacological activity of autophagy modulators on stroke under various experimental conditions.

If you would like to learn more about our services, please feel free to contact us.

1. Shi, Q., et al., The role of autophagy in the pathogenesis of ischemic stroke. Curr Neuropharmacol, 2021. 19(5): p. 629-640. 
2. Glick, D., et al., Autophagy: Cellular and molecular mechanisms. J Pathol, 2010. 221(1): p. 3-12.