New potential drug target for Alzheimer's disease
Rensselaer researchers find new potential drug target for Alzheimer's
disease

Date:
May 24, 2023
Source:
Rensselaer Polytechnic Institute
Summary:
Tau protein is implicated in many neurogenerative diseases,
including Alzheimer's. New findings point to a new potential drug
target to slow the progress of the disease: the enzymes responsible
for sulfation called heparan sulfate 3-O transferases.


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==========================================================================
FULL STORY ========================================================================== Chunyu Wang, Ph.D., professor of biological sciences at Rensselaer
Polytechnic Institute, has added to his body of research on Alzheimer's
disease with significant findings in Angewandte Chemie.

Together with his team, which includes first author and Rensselaer
doctoral student Dylan Mah, Wang performed the most comprehensive study
to date of the interactions between ApoE, or Apolipoprotein E,
and heparan sulfate (HS).

ApoE is a protein that combines with fats to transport cholesterol
throughout the body. Heparan sulfate is a sugar molecule present on cell surfaces that plays a key role in cellular communication. A variant
of ApoE, ApoE4, is the most significant genetic risk for late-onset
Alzheimer's disease.

"It's tremendously interesting to explore why ApoE4 can increase
Alzheimer's risk," said Wang.

Wang's team investigated not only ApoE4, but ApoE3, the most common
ApoE genotype and two protective isoform ApoE2 and ApoE Christchurch,
as well. They discovered that the 3-O-sulfo (3-O-S) modification of HS
was important for ApoE/HS interactions. All isoforms of ApoE recognized
3-O-S, but the differences in their strength of interactions correlated
with Alzheimer's disease risk.

"In the initial glycan array experiment, which is basically a chip with a collection of different heparan sulfate oligosaccharide on it, we flowed
ApoE over it," said Mah. "We were quite surprised to see that it had a
binding pattern that looked very similar to Tau protein. It binds very
well to the 3- O sulfated structures." Tau protein is implicated in
many neurogenerative diseases, including Alzheimer's.

The team's findings point to a new potential drug target to slow the
progress of the disease: the enzymes responsible for sulfation called
heparan sulfate 3- O transferases.

Next, the team plans to take a deeper look at ApoE/HS interaction by
developing a 3D structural model of ApoE-HS interaction and examining
this interaction in cell cultures and animal models.

"Alzheimer's disease is very complex with so many aspects," said
Wang. "The more I study it, the more interesting it gets." "Ultimately,
we want to prevent or mitigate enough of the symptoms of Alzheimer's
disease so people can continue to live independently," added Mah.

"Understanding how the disease works on a molecular basis is really
critical to finding new treatments." "As our population ages,
Dr. Wang's research on Alzheimer's disease is increasingly significant,"
said Deepak Vashishth, director of Rensselaer's Shirley Ann Jackson,
Ph.D. Center for Biotechnology and Interdisciplinary Studies, of which
Wang is a member. "The identification of a new potential drug target
to fight this progressive disease is enormously exciting for not only
the six million patients in the United States, but for their families
and caregivers." Wang and Mah were joined in research by Rensselaer Polytechnic Institute's Ashely Canning, James Gibson, Fuming Zhang, and
Robert J. Linhardt. Yongmei Xu, Xuehong Song, and Lianchun Wang of the University of South Florida contributed, along with Guowei Su and Jian
Liu of Glycan Therapeutics; Jing Zhao of China Agricultural University;
and Yongmei Xu, Eduardo Stancanelli, and Jian Liu of University of North Carolina at Chapel Hill.

* RELATED_TOPICS
o Health_&_Medicine
# Alzheimer's_Research # Healthy_Aging #
Diseases_and_Conditions
o Mind_&_Brain
# Alzheimer's # Caregiving # Dementia
o Matter_&_Energy
# Biochemistry # Organic_Chemistry # Microarrays
* RELATED_TERMS
o Prion o Excitotoxicity_and_cell_damage o
Dementia_with_Lewy_bodies o Collagen o Alzheimer's_disease o
Drug_discovery o Psychopharmacology o Enzyme

========================================================================== Story Source: Materials provided by
Rensselaer_Polytechnic_Institute. Original written by Katie
Malatino. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Dylan Mah, Yanan Zhu, Guowei Su, Jing Zhao, Ashely Canning,
James Gibson,
Xuehong Song, Eduardo Stancanelli, Yongmei Xu, Fuming Zhang,
Robert J.

Linhardt, Jian Liu, Lianchun Wang, Chunyu
Wang. Apolipoprotein E Recognizes Alzheimer's Disease
Associated 3‐ O Sulfation of Heparan Sulfate. Angewandte
Chemie International Edition, 2023; DOI: 10.1002/ anie.202212636 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2023/05/230524181929.htm

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