Alzheimer’s Disease Severity Reduced by Blocking Sugar Binding to the BACE1 Enzyme

Alzheimer’s Disease Severity Reduced by Blocking Sugar Binding to the BACE1 Enzyme
A team of researchers from Japan found that Alzheimer’s symptoms can be reduced when sugars are averted from binding to one of the disease key enzymes, named BACE1. The study entitled "An aberrant sugar modification of BACE1 blocks its lysosomal targeting in Alzheimer’s disease", was published in EMBO Molecular Medicine. Alzheimer’s disease is caused by the formation of atypical Aβ plaques in the brain when the molecule APP is abnormally cut by the enzyme BACE1. Thus, developing treatments that block BACE1 from cleaving APP is becoming an area of increasing research in Alzheimer’s disease. However, it is necessary to perform this without affecting the vital processes that are controlled by normal BACE1 activity. Yasuhiko Kizuka and colleagues from the RIKEN-Max Planck Joint Research Center determined that the binding of a specific sugar with an enzyme called GnT-III, modifies BACE1 in Alzheimer’s. The researchers hypothesized that, by preventing this process they could reduce Alzheimer’s symptoms. To do this they crossed mice without GnT-III with other mice that express human APP in the brain. The results revealed that Aβ levels and plaque formation were reduced in these mice, and improvements in cognitive performance were observed. Subsequently, the researchers demonstrated that removing the sugars of BACE1 is an effective method for inhibiting the plaque formation. By observing mice without GnT-II the researchers found lower levels of BACE1. The researchers then tested this approach without disturbing other vital processes. The mice that were lacking GnT-III were healthy, and did not exhibit higher levels of other proteins that are cleaved by BACE1, showing that targeting GnT-III avoids BACE1 from cleaving APP, and can decrease Alzheimer
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