Keqiang Ye: From Gut to Brain – Rogue Protein Fragments in Parkinson’s and Alzheimer’s Diseases

In this episode Emory University and Chinese Academy of Sciences Professor Keqiang Ye talks about his fascinating and ground-breaking trail of discoveries that have revealed previously unknown mechanism responsible for the production and accumulation of damaging fragments of the APP and Tau proteins in Alzheimer’s disease (AD) and the alpha-synuclein protein in Parkinson’s disease (PD). He discovered an enzyme called AEP that cleaves Tau and alpha-synuclein into self-aggregating toxic fragments.  Eliminating or disabling AEP can prevent the disease process and preserve brain function in mouse models of AD and PD.  More recently, in a series of studies his laboratory has provided evidence that the generation of rogue Tau and alpha-synuclein fragments first occurs in neurons surrounding the intestines and then propagates up the vagus nerve to the brain. Moreover, his group has shown that certain species of bacteria in the gut can promote the development of the disease. Finally, Professor Ye has developed drugs that inhibit AEP or activate BDNF receptors as potential treatments for AD and PD. 

LINKS

Key publications:

https://pmc.ncbi.nlm.nih.gov/articles/PMC4224595/pdf/nihms623922.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC5315368/pdf/nihms825673.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC10482867/pdf/41467_2023_Article_41283.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC8408610/pdf/EMBJ-40-e106320.pdf

https://pmc.ncbi.nlm.nih.gov/articles/PMC6951265/pdf/41422_2019_Article_241.pdf

Professor Ye’s Google Scholar page:

https://scholar.google.com/citations?user=VSP72CMAAAAJ&hl=en