New NIH donation supports single molecular study of protein key for Alzheimer’s disease

TROY, NY – A new grant from the National Institute on Aging at the National Institutes of Health will support ongoing research at the Rensselaer Polytechnic Institute to address Alzheimer’s disease caused by gene mutations. According to Chunyu Wang, the principal investigator and associate professor of biological sciences at Rensselaer, the project seeks to understand and challenge the peptide-extracting mechanism Amyloid-Beta 42 in brain cells.

“A major pathology in Alzheimer’s is the accumulation of senile plaque in the brain, which is mostly composed of Amyloid Beta-42 peptide,” said Wang, who is a member of the Rensselaer Center for Biotechnology and Interventional Studies thematic. “This donation supports the study of an enzyme responsible for the extraction of a toxic peptide using single-molecular methods, and could identify novel methods and targets for Alzheimer’s treatment in the future. “

In a cell in the brain, the enzyme gamma-secretase breaks down amyloid precursor proteins, producing either the harmless Amyloid Beta-40 peptide or the more harmful Amyloid Beta-42. In an effort to prevent the latter, Wang is working with Scott Forth, an expert in single molecular fluorescence spectroscope and assistant associate professor of biological sciences and CBIS member, to get a detailed picture of the interaction. develop.

In 2014, Wang used a nuclear magnetic resonance spectroscope to find that one of the genetic mutations found in patients with Familial Alzheimer’s Disease – which causes a small fraction of Alzheimer’s cases – causes a change that makes it more the Amyloid cutting is more likely to produce Beta-42. In an ongoing study, Wang has found drug candidates that can inhibit gamma-secretase from secreting Amyloid Beta-42 without inhibiting other important activities of the enzyme.

Forth’s knowledge provides a more detailed view of the interaction through single molecular fluorescence studies, and of the kinetics that occur during the cutting.

“Our microscopy methods allow us to track single enzymatic reactions in real time,” Forth said. “By observing one molecule at a time, we can provide new insights into the formation of Amyloid Beta you will not find using more traditional biochemical devices, which tend to provide an average over the range of possible effects. “

“Single molecular kinetic studies on gamma-secretase / substrate interactions and effects of AD-induced mutations” are funded by a $ 233,776 grant from the National Institutes of Health for one year.

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Founded in 1824, the Rensselaer Polytechnic Institute is the first technological research university in America. Rensselaer comprises five schools, 32 research centers, more than 145 academic programs, and a dynamic community made up of more than 7,900 students and more than 100,000 live alumni. Rensselaer’s faculty and alumni include more than 145 National Academy members, six members of the National Hall of Fame of Engineers, six National Technology Medal winners, five National Science Medal winners, and a Nobel Prize winner in Physics. With nearly 200 years of experience advancing scientific and technological knowledge, Rensselaer remains focused on tackling global challenges with a spirit of innovation and collaboration. To learn more, visit http: // www.rpi.edu.