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Journal Club April 19th 13:00 EST

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Dr. Oliver Medvedik will be hosting the next edition of Journal Club on Tuesday, April 19th at 13:00 EST. We will be discussing new research published in Nature where researchers modified a protein associated with Alzheimer’s disease into a more harmless form, allowing them to remove the damage caused by Alzheimer’s in human cells. This is especially important because the research was not conducted on mice but rather human cells, and shows a potential way to halt the formation of the plaques associated with Alzheimer’s in the first place.

Gain of toxic apolipoprotein E4 effects in human iPSC-derived neurons is ameliorated by a small-molecule structure corrector

Abstract

Efforts to develop drugs for Alzheimer’s disease (AD) have shown promise in animal studies, only to fail in human trials, suggesting a pressing need to study AD in human model systems. Using human neurons derived from induced pluripotent stem cells that expressed apolipoprotein E4 (ApoE4), a variant of the APOE gene product and the major genetic risk factor for AD, we demonstrated that ApoE4-expressing neurons had higher levels of tau phosphorylation, unrelated to their increased production of amyloid-β (Aβ) peptides, and that they displayed GABAergic neuron degeneration. ApoE4 increased Aβ production in human, but not in mouse, neurons. Converting ApoE4 to ApoE3 by gene editing rescued these phenotypes, indicating the specific effects of ApoE4. Neurons that lacked APOE behaved similarly to those expressing ApoE3, and the introduction of ApoE4 expression recapitulated the pathological phenotypes, suggesting a gain of toxic effects from ApoE4. Treatment of ApoE4-expressing neurons with a small-molecule structure corrector ameliorated the detrimental effects, thus showing that correcting the pathogenic conformation of ApoE4 is a viable therapeutic approach for ApoE4-related AD.

We have also covered this study in a recent article in our blog which you may want to check out.

CategoryJournal club
About the author
Oliver Medvedik

Oliver Medvedik

Oliver Medvedik, Co-founder of Genspace citizen science laboratory in Brooklyn NY, earned his Ph.D. at Harvard Medical School in the Biomedical and Biological Sciences program. As part of his doctoral work he has used single-celled budding yeast as a model system to map the genetic pathways that underlie the processes of aging in more complex organisms, such as humans. Prior to arriving in Boston for his doctoral studies, he has lived most of his life in New York City. He obtained his bachelor’s degree in biology from Hunter College, City University of New York. Since graduating from Harvard, he has worked as a biotechnology consultant, taught molecular biology to numerous undergraduates at Harvard University and mentored two of Harvard’s teams for the international genetically engineered machines competition (IGEM) held annually at M.I.T. Oliver is also the Director of The Maurice Kanbar Center for Biomedical Engineering at the Cooper Union, New York City. The Maurice Kanbar Center for Biomedical Engineering is open to all Cooper Union faculty and students working on bioengineering projects requiring equipment and space for tissue culture, genetic engineering, biomechanics, and related research. Faculty that is currently using the facility are pursuing groundbreaking biomedical research in such fields as biomedical devices, tissue engineering, obstructive sleep apnea biomechanics also collaborating with several major New York City-based hospitals. The Kanbar Center continues to provide space for undergraduate teams participating in the international genetically engineered competition (iGEM) during the summer, as well as space for courses that offer a biological laboratory component.
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