Galveston.com  UTMB Scientists Identify Enzyme Involved in Faulty Brain Cell Communication in Alzheimer's


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UTMB Scientists Identify Enzyme Involved in Faulty Brain Cell Communication in Alzheimer's

Updated 220 days ago

A new study from The University of Texas Medical Branch at Galveston has provided researchers important insights about an enzyme within the brain that plays a critical role in Alzheimer's.

The UTMB researchers found that blocking the enzyme helped prevent memory loss in mice.

The enzyme is a promising target for developing medications to prevent cognitive decline. The study was recently published in Alzheimer’s and Dementia: Translational Research and Clinical Interventions.

Thirty years of Alzheimer’s research has led to the development of therapies based on the accumulation of two proteins within the brain – beta amyloid and a toxic form of tau protein. Clinical trials that target these proteins have not enjoyed much success, so researchers have started to look for other key players in the early stages of Alzheimer’s development.

“In this study, we looked at the role of an enzyme called PLD because we know that the brains of people with Alzheimer’s have abnormally high levels of PLD activity,” said Balaji Krishnan, UTMB assistant professor in the department of neurology. “This enzyme is involved in several processes within the brain including cellular structure and border patrolling, communication between brain cells and in memory processes. We wanted to know where and how PLD levels change in Alzheimer’s.

The researchers examined donated, de-identified brain tissue confirmed to have Alzheimer’s as well as non-Alzheimer’s brains. They focused on brain regions involved in learning, memory and cognition.

They observed that one form of the enzyme called PLD1 was found at higher levels at the point of communication between brain cells in learning and memory regions of Alzheimer’s brains compared with age-matched controls.

The team blocked PLD1 in mice to see if this prevented communication between brain cells from growing dysfunctional in memory-related areas. They also had the mice perform memory tasks to search for behavioral evidence of memory problems. Some of the mice were engineered to overexpress genes for beta amyloid and toxic forms of tau, creating a model of early Alzheimer’s.

“We found that blocking PLD1 halted the cellular communication problems in the engineered mice and that PLD1 levels in memory-related regions can be increased by beta amyloid and the toxic form of tau, both known influencers of Alzheimer’s development,” Krishnan said. “This is the first time that PLD1 has been implication in dysfunctional neural communication. The new information leads us to speculate that the effects of PLD1 in memory processing may occur via toxicity by both amyloidogenic proteins dampening communication between brain cells.”

Krishnan said medications that manipulate PLD1 hold great promise for being quickly developed as an intervention in preventing Alzheimer’s-like cognitive decline. The PLD1 form of PLD is very intriguing because it manipulates two of the key culprits of Alzheimer’s development and it is inducible – meaning that PLD1 can be turned on in response to a stimulus like a medication.

Other authors include UTMB’s Rakez Kayed and Giulio Taglialatela. The work was supported by the National Institutes of Health and the UTMB Mitchell Center for Neurodegenerative Diseases. 

ABOUT THE UNIVERSITY OF TEXAS MEDICAL BRANCH
Texas' first academic health center opened its doors in 1891 and today has three campuses, four health sciences schools, four institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, a Level 1 Trauma Center and a health system offering a full range of primary and specialized medical services throughout Galveston County and the Texas Gulf Coast region. UTMB Health is an institution in the University of Texas System and a member of the Texas Medical Center. 

Article written by Raul Reyes

Raul Reyes, director of media relations at UTMB, has an extensive background in communications with more than 30 years experience in journalism. Before joining UTMB in 2007, he was an editor at The New York Times and also worked as an editor at the Dallas Morning News and the San Antonio Express-News. When he and his wife, Linda, worked at the Houston Chronicle in the 1980s, they used to dream about living and working in Galveston. Some things do come true. Raul is at UTMB and Linda edits a couple of Dallas magazines from their home in Galveston.

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