Drugs Like Metformin May Mimic Benefits of Strict Diet in Parkinson’s Patients

Researchers have discovered the molecular mechanisms behind calorie restriction’s neuroprotective effect in Parkinson’s disease, and propose a new therapeutic approach that uses existing drugs to reproduce the effects demonstrated in an animal model of the disease.

The study by Monash University Biomedicine Discovery Institute scientists, “Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson’s Disease,” was published in The Journal of Neuroscience.

Calorie restriction (CR) is a dietary intervention shown to have neuroprotective effects in Parkinson’s disease (PD). The therapeutic potential of such an approach has been reported in several papers, and demonstrated in clinical studies and various animal models of neurological disease. But the molecular mechanisms behind these effects are unclear. Such knowledge would open ways to alternative approaches that mimic the benefits observed through CR, whose dietary and lifestyle constraints are difficult to maintain over time.

Researchers found that mice on CR exhibited an increase in circulating ghrelin, the hormone that regulates hunger, and that the hormone, in turn, targets substancia nigra dopamine neurons to maintain neuronal survival. CR increased ghrelin production, preventing the development of Parkinson’s disease hallmarks.

Researchers also studied mice that did not produce the hormone despite restricted calorie intake, and found these mice exhibited more severe signs of neurodegeneration than the ghrelin-producing CR mice. This further confirmed, they said, that ghrelin is indeed responsible for the neuroprotective effect observed through CR. Moreover, activation of the protein AMPK in substancia nigra dopamine neurons is required for ghrelin-induced neuroprotection.

Researchers propose that targeting AMPK in dopamine neurons may reproduce the neuroprotective effects of CR without the need for dietary intervention, providing a novel way to possibly prevent Parkinson’s and other neurodegenerative diseases, such as Alzheimer’s.

“Once these neurodegenerative disease first appear, it should be possible to trigger the brain into thinking it is on a calorie controlled diet, in turn triggering the protective and preventative effects of Ghrelin,” Zane Andrews, the study’s leader and an associate professor at Monash, said in a press release. He specifically mentioned metformin, a type 2 diabetes drug that activates AMPK and has been shown to have neuroprotective effects in previous studies, as a potential therapeutic approach.