Catalyst Awardee

Project Description

The Liver Protects Against Aging Related Dementia

Sui Seng Tee, PhD | University of Maryland School of Medicine
Competition Sponsor: US National Academy of Medicine
Awardee Year: 2023

Parkinson’s disease (PD) affects the elderly, with devastating symptoms affecting movement and mobility. This is due to the death of brain cells, resulting in PD traditionally being viewed as a brain disorder. However, increasing evidence points to the involvement of the intestines. PD patients have mutated proteins called alpha-synuclein that are improperly folded. These proteins have also been found in the intestines, leading to experts to believe PD may originate from food or the environment. The intestines are connected to the liver by a major blood vessel called the portal vein. The liver plays an important role in removing toxins from blood, in a process called autophagy. Autophagy can be seen as ‘housekeeping’, recycling toxins into useful molecules for liver cells. This proposal studies the role of the liver in PD. We believe that the liver plays a protective role, detoxifying mutant alpha-synuclein from the intestines to delay spread to the brain. We test this assumption in mice, where mutant alpha-synuclein is directly injected into the gut. Alpha-synuclein is expected to travel from the gut to the brain, passing through the liver. We will measure traces of the mutant protein in the liver, followed by blocking gut-to-liver spread by surgically ligating the portal vein. Finally, we use genetic methods and drugs to up-regulate autophagy in the liver, expecting a delay in gut-to-brain spread of mutant alpha-synuclein. If successful, these experiments lay the groundwork for future drugs that target the liver, to prevent or delay the debilitating symptoms of PD.

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