Summary of Researchers Solve One Piece of Alzheimer’s Puzzle:
Researchers from Drexel University have discovered a new brain regulation mechanism that may be an early contributor to Alzheimer’s disease. The Akanksha Bhatnagar and Felice Elefant team found that the Tip60 enzyme plays a crucial role in RNA splicing, generating protein diversity required for learning and memory. The team also found that restoring depleted amounts of Tip60 in Alzheimer’s models not only rescued gene activation but also partially protected against splicing disruptions, demonstrating that the Tip60 enzyme can be a drug target to protect against Alzheimer’s. The findings could lead to significant developments in drug design and the treatment of Alzheimer’s.
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New Study Sheds Light on the Role of Tip60 Enzyme in Alzheimer’s Disease
Alzheimer’s is a progressive neurodegenerative disorder affecting memory, thinking, and behavior. It is the most common cause of dementia in older adults. There is no cure for Alzheimer’s, but researchers from Drexel University have made a breakthrough in understanding the disease through their studies on the Tip60 enzyme.
A Crucial Brain Regulation Mechanism that Contributes to Alzheimer’s
A team of scientists from Drexel University has discovered a new brain regulation mechanism crucial in producing the proper proteins that maintain optimal brain health. The malfunctioning of this mechanism may be an early contributor to Alzheimer’s disease.
The Versatility of Brain Cells
The brain’s ability to constantly adapt to new stimuli and form new memories is due to the versatility of brain cells. These cells can generate various functional versions of the same protein through a process known as alternative RNA splicing.
RNA Splicing and its Disruption in Alzheimer’s Disease
Recent studies have reported defects in RNA splicing of genes in the brains of Alzheimer’s patients, which has led to the conclusion that splicing disruptions are considered an indicator of Alzheimer’s disease. The causes for these splicing disruptions in the brain are still unknown, which has hindered the development of treatments focused on this defect.
Tip60 Enzyme’s Role in Binding to Certain RNA in the Brain
The team led by Akanksha Bhatnagar and Felice Elefant, biology researchers in Drexel’s College of Arts and Sciences, is the first to uncover the role of the Tip60 enzyme in binding to specific RNA in the brain to control how they are spliced. Tip60’s novel function is a critical piece in the brain puzzle that brings us one step closer to understanding the big picture behind Alzheimer’s Disease.
Restoration of the Enzyme Tip60 Reversed Symptoms in an Alzheimer’s Model System
A 2018 Drexel study by Elefant’s lab showed that restoring the enzyme Tip60 balanced the enzymes in the brain and reversed symptoms in an Alzheimer’s model system. Building on that study, Elefant, Bhatnagar, and their team discovered that Tip60 regulates gene activation to make RNA and regulates how RNA is spliced to generate diverse protein variants, which has been shown to contribute to the reversal of Alzheimer’s symptoms.
Restoring Depleted Amounts of Tip60 in Alzheimer’s Models
The researchers found that restoring depleted amounts of Tip60 in Alzheimer’s models not only rescues gene activation but also partially protects against splicing disruptions — demonstrating that the Tip60 enzyme can be a drug target to protect against two different processes that go awry in Alzheimer’s.
Environmental Changes Impacting Alzheimer’s Disease
The Elefant Lab at Drexel also explores how environmental changes can impact Alzheimer’s disease. “More than 95% of Alzheimer’s cases do not have a clear genetic link with parents; they are arising sporadically due to external factors or epigenetics,” said Bhatnagar. “We want to know how and why environmental changes can impact Alzheimer’s, and one of the ways this can happen is through the enzyme we study, Tip60.”
The Bottom Line
These findings could lead to significant developments in drug design and the treatment of Alzheimer’s, according to the team. “If we can figure out what genes are being altered before deficits occur, there is a possibility that these RNA variations could serve as biomarkers to identify Alzheimer’s disease early on,” said Bhatnagar. This study was funded by the National Institutes of Neurological Disorders and Stroke of the NIH.
