Alzheimer’s and Neurodegenerative Disease Treatment
A pharmaceutical compound consisting of stable glutathione (GSH) analogs has been developed to treat Alzheimer's disease (AD) and other neurodegenerative disorders. The GSH analogs fulfill key roles of endogenous GSH and resist enzyme breakdown while acting as a substrate for the detoxifying enzyme glyoxalase-I.
Decreases Glycation and Amyloid-beta Plaques
The GSH analogs treat AD through two mechanisms. Amyloid-beta (Aβ) plaques, a hallmark of AD and other neurodegenerative diseases, are caused by Aβ protein aggregation. Aβ aggregation is induced through glycation. Glyoxalase-I curbs glycation; but this process is dependent on GSH, which is severely depleted in an AD-affected brain. The new GSH analogs treat AD progression by restoring glyoxalase-I activity in the brain, which decreases glycation, and hampers glycation-induced Aβ aggregation, and in turn, plaque formation.
Neutralizes Oxidative Stress
The GSH analogs are able to pass through the blood-brain barrier to neutralize oxidative stress in the brain. Oxidative stress is a root cause of neurodegenerative disorders, as well as other diseases.
Replicates Endogenous GSH Activity
The new GSH analogs are the first compounds to replicate endogenous GSH activity while resisting breakdown. Other compounds which have tried to mimic the role of GSH failed because they were not resistant to breakdown. This treatment could be used in conjunction with other AD treatments, or used independently. This AD treatment can be used earlier than any other existing treatments.
Separately, the GSH analogs were found to have hepatoprotective qualities. The analogs react directly with N-acetyl-p-benzoquinoneimine (NAPQI), a toxic by-product produced during acetaminophen metabolism. Using the GSH analogs in combination with acetaminophen could improve overall safety. The analogs could also act as a rescue treatment for acute acetaminophen overdose.
BENEFITS AND FEATURES OF GSH ANALOGS COMPOUND:
- Helps prevent harmful glycation and Aβ plaque formation
- Treats AD earlier than other treatments
- Can be used in combination with other treatments or independently
- Antioxidant properties treats root cause of neurodegenerative disease
- Has hepatoprotective qualities and could be used with acetaminophen
Phase of Development In vitro and in vivo data available
Researchers: Swati More, PhD Assistant Professor, Center for Drug Design