Abstract Title

The Role of BHMT in the Progression of Neurodegenerative Symptoms

Abstract

Causes of neurodegenerative diseases, such as multiple sclerosis (MS), have been attributed to an increase in oxidative stress, and this increased level of stress leads to the downregulation of the folate-vitamin B12 pathway. This downregulation inhibits gene expression by disrupting the methionine metabolism cycle, decreasing the amount of methylation occurring in cells. A possible mechanism that could be utilized to reduce the progression of MS is the induction of a separate methylation pathway independent from the folate-vitamin B12 cycle by using the enzyme betaine-homocysteine methyltransferase (BHMT), which methylates homocysteine back to methionine with betaine. BHMT is found in the nucleus of both primary neurons and oligodendrocytes and can influence gene expression. To test this hypothesis, we sought to examine how different treatments affect the way BHMT binds to chromatin to obtain a deeper understanding of how this alters gene expression. Specifically, we wanted to see the ways in which BHMT binding was altered through exposure to varying degrees of oxidative stress. This allowed us to identify which treatments caused BHMT to bind more tightly to the chromatin and therefore determine which of the conditions play the most important role in chromatin remodeling. Our data suggest these changes in gene expression are involved in MS pathology.

Modified Abstract

Causes of multiple sclerosis (MS) have been attributed to an increase in oxidative stress, which leads to downregulation of the folate-vitamin B12 pathway and decreases cellular methylation. Induction of a separate methylation pathway independent from the folate-vitamin B12 cycle using the enzyme betaine-homocysteine methyltransferase (BHMT), which influences gene expression, could be used to decrease progression of MS symptoms. We sought to examine how different treatments affect the way BHMT binds to chromatin to obtain a deeper understanding of how this alters gene expression. The ways in which BHMT binding was altered through exposure to varying degrees of oxidative stress allowed us to identify which treatments caused the most chromatin remodeling. Our data suggest these changes in gene expression are involved in MS pathology.

Research Category

Biology/Ecology

Primary Author's Major

Biology

Mentor #1 Information

Sarah

Sternbach

Mentor #2 Information

Dr. Jennifer

McDonough

Mentor #3 Information

Dr. Ernest

Freeman

Start Date

April 2019

Research Area

Molecular and Cellular Neuroscience

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Apr 9th, 1:00 PM

The Role of BHMT in the Progression of Neurodegenerative Symptoms

Causes of neurodegenerative diseases, such as multiple sclerosis (MS), have been attributed to an increase in oxidative stress, and this increased level of stress leads to the downregulation of the folate-vitamin B12 pathway. This downregulation inhibits gene expression by disrupting the methionine metabolism cycle, decreasing the amount of methylation occurring in cells. A possible mechanism that could be utilized to reduce the progression of MS is the induction of a separate methylation pathway independent from the folate-vitamin B12 cycle by using the enzyme betaine-homocysteine methyltransferase (BHMT), which methylates homocysteine back to methionine with betaine. BHMT is found in the nucleus of both primary neurons and oligodendrocytes and can influence gene expression. To test this hypothesis, we sought to examine how different treatments affect the way BHMT binds to chromatin to obtain a deeper understanding of how this alters gene expression. Specifically, we wanted to see the ways in which BHMT binding was altered through exposure to varying degrees of oxidative stress. This allowed us to identify which treatments caused BHMT to bind more tightly to the chromatin and therefore determine which of the conditions play the most important role in chromatin remodeling. Our data suggest these changes in gene expression are involved in MS pathology.