{"id":11019,"date":"2024-06-10T09:11:34","date_gmt":"2024-06-10T14:11:34","guid":{"rendered":"https:\/\/www.wisconsin.edu\/all-in-wisconsin-new\/?post_type=campus_story&p=11019"},"modified":"2024-06-10T09:11:34","modified_gmt":"2024-06-10T14:11:34","slug":"uw-madison-research-nanomaterial-that-mimics-proteins-could-be-basis-for-new-neurodegenerative-disease-treatments","status":"publish","type":"campus_story","link":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/story\/uw-madison-research-nanomaterial-that-mimics-proteins-could-be-basis-for-new-neurodegenerative-disease-treatments\/","title":{"rendered":"UW-Madison research: Nanomaterial that mimics proteins could be basis for new neurodegenerative disease treatments"},"content":{"rendered":"
\"Photo<\/a>
Jeffrey and Delinda Johnson work in their lab on the UW\u2013Madison campus. Photo by Sally Griffith-Oh\/UW\u2013Madison<\/figcaption><\/figure>\n

A newly developed nanomaterial that mimics the behavior of proteins could be an effective tool for treating Alzheimer\u2019s and other neurodegenerative diseases. The nanomaterial alters the interaction between two key proteins in brain cells \u2014 with a potentially powerful therapeutic effect.<\/p>\n

The innovative findings,\u00a0recently published in the journal Advanced Materials<\/a>, were made possible thanks to a collaboration between University of Wisconsin\u2013Madison scientists and nanomaterial engineers at Northwestern University.<\/p>\n

The work centers around altering the interaction between two proteins that are believed to be involved in setting the stage for diseases like Alzheimer\u2019s, Parkinson\u2019s and amyotrophic lateral sclerosis, or ALS.<\/p>\n

The first protein is called Nrf2, a specific type of protein called a transcription factor that turns genes on and off within cells.<\/p>\n

\"Image<\/a>
This image shows the effect of protein-like polymers (red) in the brain cells of a mouse model. The nanoscale polymers are designed to alter the interaction between two proteins to combat oxidative stress in the cells. Image courtesy of Johnson Lab\/UW\u2013Madison<\/figcaption><\/figure>\n

One of Nrf2\u2019s important functions is its antioxidant effect. While different neurodegenerative diseases result from separate disease processes, a commonality among them is the toxic effect of oxidative stress on neurons and other nerve cells. Nrf2 combats this toxic stress in brain cells, helping to stave off disease.<\/p>\n

Jeffrey Johnson<\/a>, a professor in the UW\u2013Madison School of Pharmacy, has been studying Nrf2 as a promising target for treating neurodegenerative diseases for decades alongside his wife\u00a0Delinda Johnson<\/a>, a senior scientist at the pharmacy school. In 2022, the Johnsons and another group of collaborators found that increasing Nrf2 activity in a specific cell type in the brain, the astrocyte,\u00a0helped protect neurons in mouse models of Alzheimer\u2019s disease<\/a>, leading to significantly less memory loss.<\/p>\n

While this previous research suggested that increasing Nrf2\u2019s activity could form the basis of an Alzheimer\u2019s treatment, scientists have found it challenging to effectively target the protein within the brain.<\/p>\n

\u201cIt\u2019s hard to get drugs into the brain, but it\u2019s also been very hard to find drugs that activate Nrf2 without a lot of off-target effects,\u201d says Jeffrey Johnson.<\/p>\n

Enter the new nanomaterial. Known as a protein-like polymer, or PLP, the synthetic material is designed to bind to proteins as if it were itself a protein. This nano-scale imitator is a product of a team led by Nathan Gianneschi, a professor of chemistry at Northwestern and faculty member at the university\u2019s\u00a0International Institute for Nanotechnology<\/a>.<\/p>\n

Gianneschi has designed multiple PLPs to target various proteins. This particular PLP is structured to alter the interaction between Nrf2 and another protein called Keap1. The proteins\u2019 interaction, or pathway, is a well-known target for treating many conditions because Keap1 essentially controls when Nrf2 responds to \u2014 and combats \u2014 oxidative stress. Bound together under unstressed conditions, Keap1 releases Nrf2 to do its antioxidant work when needed.<\/p>\n

Gianneschi and the Johnsons were connected via Robert Pacifici, chief science officer at the\u00a0CHDI Foundation<\/a>, which funds research aimed at treating Huntington\u2019s disease, another neurodegenerative condition. The foundation has funded both the Johnsons\u2019 and Gianneschi\u2019s work in the past.<\/p>\n

\u201cJust in passing, Nathan and his colleagues at Grove Biopharma, a preclinical biotech startup focused on therapeutic targeting of protein-protein interactions, said to Robert that they were thinking about moving to target Nrf2,\u201d says Johnson. \u201cAnd Robert said, \u2018If you\u2019re going to do that, you should call Jeff Johnson.’\u201d<\/p>\n

Soon, the Johnsons and Gianneschi were discussing the possibility of the UW\u2013Madison lab providing mouse model brain cells needed to test Gianneschi\u2019s protein-like nanomaterial.<\/p>\n

Jeffrey Johnson says he was initially somewhat skeptical about the PLP approach, given his unfamiliarity with it and the general difficulty of precisely targeting proteins in brain cells.<\/p>\n

\u201cBut then one of Nathan\u2019s students came up here with it and put it on our cells, and I\u2019ll be damned if it didn\u2019t work really well,\u201d he says. \u201cWe really dove into it then.\u201d<\/p>\n

The resulting research showed that Gianneschi\u2019s PLP was very effective at binding to Keap1, which freed up Nrf2 to accumulate in cells\u2019 nuclei, amping up its antioxidant function. Importantly, it did so without causing the unwanted off-target effects that have hampered other strategies aimed at better activating Nrf2.<\/p>\n

While that work was performed in cells in culture, the Johnsons and Gianneschi are now taking it a step further in mouse models of neurodegenerative diseases. It\u2019s a line of research that they hadn\u2019t expected to be involved in but are now excited to be pursuing.<\/p>\n

\u201cWe don\u2019t have the expertise in biomaterials,\u201d says Delinda Johnson. \u201cSo getting that from Northwestern and then moving forward on the biological side here at UW shows that these types of collaborations are really important.\u201d<\/p>\n

\n

Written by Will Cushman<\/p>\n

Link to original story: https:\/\/news.wisc.edu\/nanomaterial-that-mimics-proteins-could-be-basis-for-new-neurodegenerative-disease-treatments\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

A newly developed nanomaterial that mimics the behavior of proteins could be an effective tool for treating Alzheimer\u2019s and other neurodegenerative diseases. The nanomaterial alters the interaction between two key proteins in brain cells \u2014 with a potentially powerful therapeutic effect. The innovative findings,\u00a0recently published in the journal Advanced Materials, were made possible thanks to […]<\/p>\n","protected":false},"author":15,"featured_media":11022,"comment_status":"closed","ping_status":"closed","template":"","institution":[103],"story_category":[],"class_list":["post-11019","campus_story","type-campus_story","status-publish","has-post-thumbnail","hentry","institution-uw-madison"],"_links":{"self":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/campus_story\/11019","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/campus_story"}],"about":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/types\/campus_story"}],"author":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/users\/15"}],"replies":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/comments?post=11019"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/media\/11022"}],"wp:attachment":[{"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/media?parent=11019"}],"wp:term":[{"taxonomy":"institution","embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/institution?post=11019"},{"taxonomy":"story_category","embeddable":true,"href":"https:\/\/www.wisconsin.edu\/all-in-wisconsin\/wp-json\/wp\/v2\/story_category?post=11019"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}