MSGID: 1:317/3 646ee4b9   
   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    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   
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   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   
      
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   Story Source: Materials provided by   
   Rensselaer_Polytechnic_Institute. Original written by Katie   
   Malatino. Note: Content may be edited for style and length.   
      
      
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   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   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/05/230524181929.htm   
      
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