Tomatidine protects against ischemic neuronal injury by improving lysosomal function

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Cerebral ischemia is a severe neurological disorder with limited therapeutic options.
• Autophagy, an intracellular degradation process, shows neuroprotective effects against ischemic neuronal injury.
• Tomatidine, a metabolite from unripe tomatoes, activates autophagy but its neuroprotective role in cerebral ischemia is unknown.

Purpose of the Study:

• To investigate the potential neuroprotective effects of tomatidine against oxygen-glucose deprivation/reperfusion (OGD/R)-induced ischemic injury in neuronal cells.
• To elucidate the underlying mechanisms of tomatidine's action, focusing on autophagy and lysosomal pathways.

Main Methods:

• N2a cells and primary mouse cortical neurons were subjected to OGD/R.
• Cell injury was assessed using MTT assay and lactate dehydrogenase release.
• Autophagy and lysosomal activity were analyzed via LC3 visualization, Western blotting (LC3, Cathepsin D, Cathepsin B, TFEB), and lysosomal staining (LysoTracker Red, DQ-BSA red).

Main Results:

• Tomatidine alleviated OGD/R-induced injury in neuronal cells.
• Tomatidine treatment reduced OGD/R-elevated LC3-II levels, indicating enhanced lysosomal degradation rather than increased autophagosome formation.
• Tomatidine increased lysosome number, proteolytic activity, Cathepsin D and B expression, and TFEB nuclear translocation, suggesting enhanced lysosomal function.

Conclusions:

• Tomatidine exhibits neuroprotection against ischemic injury by promoting lysosomal activity.
• The protective mechanism involves enhanced lysosomal degradation and potentially TFEB-mediated pathways.
• Tomatidine represents a potential therapeutic agent for cerebral ischemia by targeting lysosomal function.