Bioengineers from the University of California, San Diego developed an explanation for why some types of neurons die sooner than others in the brains of people with Alzheimer's disease. These insights, published in the journal Nature Biotechnology on November 21, come from detailed models of brain energy metabolism developed in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering.
The Alzheimer's insights demonstrate how fundamental insights on human metabolism can be gleaned from computer models that incorporate large genomic and proteomic data sets with information from biochemical studies. UC San Diego bioengineering professor Bernhard Palsson and his students and collaborators first developed this "in silico" modeling approach for E. coli and other prokaryotes, and later extended it to human tissues.
The Nature Biotechnology paper describes the first time this modeling approach has been used to capture how the metabolism of specific human cell types affect the metabolism of other cell types.
"In human tissues, different cells have different roles. We're trying to predict how the behavior of one cell type will affect the behavior of other cell types," said Nathan Lewis, a Ph.D. candidate in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering and the first author on the Nature Biotechnology paper, which also includes authors from the University of Heidelberg, Massachusetts Institute of Technology, and the German Cancer Research Center (DKFZ).
Similar approaches can be used to identify potential off-target effects of drugs, provide insights on disease progression, and offer new tools for uncovering the underlying biological mechanisms in a wide range of human tissues and cell types.
Why Some Neurons Die First in the Alzheimer's Brain
In the brains of people with Alzheimer's disease, certain cells, such as glutamatergi
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University of California - San Diego