Ginsenoside Rg1 ameliorates Alzheimer's disease pathology via restoring mitophagy

Area of Science:

• Neuroscience
• Cell Biology
• Pharmacology

Background:

• Alzheimer's disease (AD) is a prevalent dementia characterized by impaired mitophagy, a crucial mitochondrial quality control process.
• Ginsenoside Rg1 (Rg1), a compound from Ginseng, exhibits neuroprotective properties relevant to AD.
• The specific role of Rg1 in regulating mitophagy in AD remains largely unexplored.

Purpose of the Study:

• To investigate the potential of Rg1 to ameliorate AD pathology by modulating mitophagy.
• To elucidate the underlying molecular mechanisms, particularly the involvement of the PINK1/Parkin pathway.

Main Methods:

• Utilized human SH-SY5Y cells and a 5XFAD mouse model of AD.
• Treated cells and mice with Rg1 and assessed mitophagy markers via western blot and immunofluorescence.
• Evaluated cognitive function using the Morris water maze and observed mitophagic events using electron microscopy.

Main Results:

• Rg1 treatment restored mitophagy and improved memory deficits in AD cellular and mouse models.
• Rg1 activated the PINK1/Parkin pathway, a key regulator of mitophagy.
• Rg1 potentially enhanced microglial phagocytosis, leading to reduced amyloid-beta deposition in the hippocampus.

Conclusions:

• Ginsenoside Rg1 demonstrates neuroprotective effects in AD models through the induction of PINK1-Parkin mediated mitophagy.
• Rg1 ameliorates cognitive impairments in 5XFAD mice, highlighting its therapeutic potential for Alzheimer's disease.