Nav: Home

Researchers discover potential new therapeutic target for Alzheimer's disease

June 12, 2019

TAMPA, Fla. (June 12, 2019) -- Apolipoproten E (apoeE) is a major genetic risk factor for the development of Alzheimer's disease, yet the protein tends to be understudied as a potential druggable target for the mind-robbing neurodegenerative disease.

Now a research team led by the University of South Florida Health (USF Health) Morsani College of Medicine reports that a novel apoE antagonist blocks apoE interaction with N-terminal amyloid precursor protein (APP). Moreover, this peptide antagonist, known as 6KApoEp, was shown to reduce Alzheimer's-associated beta amyloid (β-amyloid) accumulation and tau pathologies in the brain, as well as improving learning and memory in mice genetically engineered to mimic symptoms of Alzheimer's disease.

Many failed anti-amyloid therapies for Alzheimer's disease have been directed against various forms of the protein β-amyloid, which ultimately forms clumps of sticky plaques in the brain. The presence of these amyloid plaques is one of the major hallmarks of Alzheimer's disease.

The USF Health research findings suggests that disrupting apoE physical interaction with N-terminal APP may be a new disease-modifying therapeutic strategy for this most common type of dementia.

The preclinical study was published online May 2 in Biological Psychiatry.

"For the first time, we have direct evidence that the N-terminal section of apoE itself acts as an essential molecule (ligand) to promote the binding of apoeE to the N-terminal region of APP outside the nerve cell," said the study's lead author Darrell Sawmiller, PhD, an assistant professor in the USF Health Department of Psychiatry & Behavioral Neurosciences. "This receptor-mediated mechanism plays a role in the development of Alzheimer's disease. Overstimulation of APP by apoE may be an earlier, upstream event that signals other neurodegenerative processes contributing to the amyloid cascade."

"Initially we wanted to better understand how apoE pathologically interacts with APP, which leads to the formation of β-amyloid plaques and neuronal loss," said study senior author Jun Tan, PhD, MD, a professor in the USF Health Department of Psychiatry & Behavioral Neurosciences. "Our work further discovered an apoE derivative that can modulate structural and functional neuropathology in Alzheimer's disease mouse models."
-end-
Alzheimer's disease is a global epidemic, afflicting an estimated 50 million people worldwide and 5.8 million in the U.S, according to the Alzheimer's Association. With the aging of the Baby Boomer generation, the prevalence of the debilitating disease is expected to increase dramatically in the coming years. Currently, no treatments exist to prevent, reverse or halt the progression of Alzheimer's disease, and current medications may only relieve dementia symptoms for a short time.

Dr. Sawmiller, Ahsan Habib, PhD, and Lucy (Hauyan) Hou, MD, of the USF Health Department of Psychiatry and Behavioral Neurosciences (all lead authors) collaborated with colleagues from the Laboratory of Neurosciences at the National Institute on Aging (NIA), the Department of Neuroscience at Johns Hopkins University School of Medicine, the USF Center for Neurosurgery and Brain Repair, and Saitama Medical University in Japan. Other study authors included Takashi Mori, PhD; Anran Fan, PhD; Jun Tian, BS; Brian Giunta, MD, PhD; Paul R. Sanberg, PhD; and Mark P. Mattson, PhD.

The research was supported by an NIA grant from the National Institutes of Health.

University of South Florida (USF Innovation)

Related Protein Articles:

Protein aggregation: Protein assemblies relevant not only for neurodegenerative disease
Amyloid fibrils play a crucial role in neurodegenerative illnesses. Scientists from Heinrich Heine University Düsseldorf (HHU) and Forschungszentrum Jülich have now been able to use cryo-electron microscopy (cryo-EM) to decode the spatial structure of the fibrils that are formed from PI3K SH3 domains - an important model system for research.
Old protein, new tricks: UMD connects a protein to antibody immunity for the first time
How can a protein be a major contributor in the development of birth defects, and also hold the potential to provide symptom relief from autoimmune diseases like lupus?
Infection-fighting protein also senses protein misfolding in non-infected cells
Researchers at the University of Toronto have uncovered an immune mechanism by which host cells combat bacterial infection, and at the same time found that a protein crucial to that process can sense and respond to misfolded proteins in all mammalian cells.
Quorn protein builds muscle better than milk protein
A study from the University of Exeter has found that mycoprotein, the protein-rich food source that is unique to Quorn products, stimulates post-exercise muscle building to a greater extent than milk protein.
More than a protein factory
Researchers from the Stowers Institute for Medical Research have discovered a new function of ribosomes in human cells that may show the protein-making particle's role in destroying healthy mRNAs, the messages that decode DNA into protein.
More Protein News and Protein Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#537 Science Journalism, Hold the Hype
Everyone's seen a piece of science getting over-exaggerated in the media. Most people would be quick to blame journalists and big media for getting in wrong. In many cases, you'd be right. But there's other sources of hype in science journalism. and one of them can be found in the humble, and little-known press release. We're talking with Chris Chambers about doing science about science journalism, and where the hype creeps in. Related links: The association between exaggeration in health related science news and academic press releases: retrospective observational study Claims of causality in health news: a randomised trial This...