{"id":111461,"date":"2025-08-26T14:32:07","date_gmt":"2025-08-26T14:32:07","guid":{"rendered":"https:\/\/www.newsbeep.com\/us\/111461\/"},"modified":"2025-08-26T14:32:07","modified_gmt":"2025-08-26T14:32:07","slug":"novel-enzyme-activator-discovered-as-potential-alzheimers-disease-therapy","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/us\/111461\/","title":{"rendered":"Novel Enzyme Activator Discovered as Potential Alzheimer\u2019s Disease Therapy"},"content":{"rendered":"

Researchers from Drexel University\u2019s College of Arts and Sciences<\/a> and College of Medicine<\/a> have found a potential new therapeutic target for Alzheimer\u2019s disease. Expanding on their previous research on Tip60 histone acetyltransferase (HAT), known as the Tip60 enzyme<\/a>, which controls genes that promote learning and memory in the brain, the Drexel research team generated small molecular compounds that activate Tip60 and restore deficits in the brain found in Alzheimer\u2019s disease patients, such as gene expression programs linked to learning, memory and neurodegeneration. The study was published in Nature Communications<\/a>.<\/p>\n

\u201cMany studies on Alzheimer’s disease are focused on genetic causes,\u201d said Felice Elefant, PhD<\/a>, a professor in the College of Arts and Sciences. \u201cBut research has shown that over 90% of the causes<\/a> of Alzheimer’s disease cases are actually sporadic in nature, with severity dependent upon a complex interplay of genetics, age and environmental factors orchestrated in large part by neuroepigenetic \u2013 dynamic and reversible \u2013 mechanisms of gene control.\u201d\u00a0<\/p>\n

Elefant added that because neuroepigenetic gene regulation in the brain is influenced by our external experiences, lifestyle choices and even the foods we eat, her lab explores how such neuroepigenetic gene control mechanisms go awry as people age, culminating into age related neurodegenerative disorders that include Alzheimer\u2019s disease.<\/p>\n

Elefant explained that in multiple neurodegenerative disorders, such as Alzheimer’s disease, Parkinson\u2019s diseases and Amyotrophic Lateral Sclerosis (ALS), these neuroepigenetic gene control processes are not playing the role that they should be, leading to losses in memory and other cognitive functions.<\/p>\n

Neuroepigenetic gene control is moderated by acetylation \u2013 or a reaction \u2013 of histone proteins in the brain that control chromatin (DNA and protein) packaging. DNA is wound around these histones to form a compact chromatin state that is resistant to genes being turned on. The histone proteins are marked for acetylation causing chromatin to loosen, enabling DNA to become accessible for gene activation. But, Elefant explained, in age-related neurodegenerative disorders, like Alzheimer\u2019s disease, there’s a reduction of certain histone acetyltransferase (HAT) enzymes that \u201cwrite\u201d these histone acetylation marks, resulting in reduced histone acetylation in the brain that causes cognition genes to be turned off. One such specific HAT enzyme is called Tip60, which adds specific acetylation marks that are responsible for turning on the genes that promote learning and memory. In Alzheimer\u2019s disease patient\u2019s postmortem brains, they have found that the Tip60- HAT enzyme is significantly reduced.<\/p>\n

Elefant went on to explain that by genetically increasing Tip60 in Drosophila \u2013 fruit fly \u2013 brains that model human Alzheimer\u2019s disease, they observed reactivation of inappropriately turned off cognition linked genes and prevention of multiple neural processes impaired in Alzheimer\u2019s disease, including learning and memory, early lethality, plaque formation and neurodegeneration.\u00a0<\/p>\n

\u201cOur goal with this study was to develop a novel compound that specifically interacts with human Tip60 to enhance its HAT activity,\u201d said Elefant. \u201cWe speculate these compounds will be useful in activating the residual Tip60 that’s left in a patient\u2019s brain with Alzheimer\u2019s disease to restore cognition-linked gene expression profiles that, in turn, alleviate cognitive deficits and slow neurodegeneration progression.\u201d<\/p>\n

Most Alzheimer\u2019s disease neuroepigenetic therapy research has focused on inhibiting the enzymes that remove histone acetylation. Although inhibitors are easier to develop, explained Elefant, blocking enzymes can cause non-specific hyperacetylation that further impairs cognition. In contrast, generating selective Tip60 activators for Alzheimer\u2019s disease enables site specific, cognition-linked acetylation marks to be maintained, allowing for a more specific neuroepigenetic based therapeutic that does not cause detrimental side-effects.\u00a0<\/p>\n

According to Elefant, small molecular compounds that specifically activate Tip60 have never been developed before. Elefant\u2019s collaborators, Akanksha Bhatnagar, PhD, a postdoctoral researcher at the University of Pennsylvania, and Sandhya Kortagere, PhD<\/a>, a professor in Drexel\u2019s College of Medicine, created the compound by using a computational virtual screening of molecules \u2013 known as pharmacophore-based virtual screening \u2013 to find one that can bind and theoretically activate Tip60\u2019s HAT domain, then had the compound manufactured and tested in a fruit fly that models human Alzheimer\u2019s disease.<\/p>\n","protected":false},"excerpt":{"rendered":"Researchers from Drexel University\u2019s College of Arts and Sciences and College of Medicine have found a potential new…\n","protected":false},"author":2,"featured_media":111462,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[50],"tags":[200,79],"class_list":["post-111461","post","type-post","status-publish","format-standard","has-post-thumbnail","category-genetics","tag-genetics","tag-science"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/111461","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/comments?post=111461"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/posts\/111461\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media\/111462"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/media?parent=111461"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/categories?post=111461"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/us\/wp-json\/wp\/v2\/tags?post=111461"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}