New research identifies key contributor to Alzheimer's disease process

Nov 14, 2008

Walter J. Lukiw, PhD, Associate Professor of Neuroscience and Ophthalmology at LSU Health Sciences Center New Orleans, is the lead author of a paper identifying, for the first time, a specific function of a fragment of ribonucleic acid (RNA), once thought to be no more than a byproduct, in regulating inflammation and the development of Alzheimer's disease.

The paper, An NF-kB-sensitive micro RNA-146a-mediated inflammatory circuit in Alzheimer's disease and in stressed human brain cells, will be published in the November 14, 2008 issue of The Journal of Biological Chemistry.

Dr. Lukiw's lab at the LSU Health Sciences Center New Orleans Neuroscience Center of Excellence has shown that this tiny piece of RNA, or microRNA, called miRNA-146a is found in increased amounts in stressed human brain cells and in Alzheimer's disease, and that it plays a crucial role in the regulation of inflammation and disease-related neuropathology thought to be integral to the Alzheimer's disease process.

Dr. Lukiw's research team, which also included LSUHSC's Jian Guo Cui, MD, PhD and Yuhai Zhao, a post doctoral student in the lab, demonstrated in human brain cells in primary culture that MiRNA-146a targets the messenger RNA of an important anti-inflammatory regulator called complement factor H (CFH). Testing both control cells and Alzheimer's disease-affected tissues, they found that miRNA-164a appears to reduce the amount and bioavailability of CFH, promoting the inflammation of brain cells and contributing to the development of Alzheimer's disease.

The most common form of dementia, Alzheimer's Disease is a fatal, age-related neurodegenerative disorder characterized clinically by the progressive erosion of cognition and memory, and neuropathologically by defective gene expression and increased inflammatory cell signaling. According to the Alzheimer's Foundation of America, it is estimated that Alzheimer's disease currently affects more than 5 million Americans and it is projected that the number could more than triple to 16 million by mid-century.

"The goal of these neuroscience research studies is to further our understanding of the molecular biology and genetic mechanisms associated with Alzheimer's Disease and to advance the design of therapeutic strategies to counteract this common and tragic neurological disorder," said Dr. Lukiw.

Source: Louisiana State University Health Sciences Center

Explore further: Losing weight may ease chronic heartburn

add to favorites email to friend print save as pdf

Related Stories

Space experiment sheds light on immune struggles

Apr 22, 2013

A lab experiment that rode to space two years ago has offered new clues about why astronauts' immune systems struggle to perform in zero gravity, US military researchers said on Monday.

Fast track to mouse modeling

Apr 02, 2013

What genes are responsible for the development of breast cancer? What are the brain cell mutations that lead to the onset of Alzheimer's? To find new therapies, scientists have to understand how diseases ...

Recommended for you

ATS: Early prone positioning reduces mortality in ARDS

1 hour ago

(HealthDay)—For patients with acute respiratory distress syndrome (ARDS), prolonged prone positioning during mechanical ventilation is associated with significantly reduced mortality at 28 and 90 days, ...

No new H7N9 cases in China for a week

2 hours ago

No new human cases of the H7N9 virus have been recorded in China for a week, national health authorities said, for the first time since the outbreak began in March.

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

superhuman
not rated yet Nov 14, 2008
New research identifies key contributor to Alzheimer's disease process


Lies. They don't identify key contributor, they research one of the many differences between cells form healthy patients and from patients with with Alzheimer's disease. Patients with Alzheimer's disease have more of a specific molecule (miRNA). Authors of the paper test this molecule and find that it inhibits cells inflammatory pathway.

This molecule can be a contributor or it can be a consequence of the disease. Even if it is a contributor nothing is known about the reason for its upregulation.

Here is the abstract:

Human brains retain discrete populations of micro RNA (miRNA) species that support homeostatic brain gene expression functions; however, specific miRNA abundance is significantly altered in neurological disorders such as Alzheimer disease (AD) when compared with age-matched controls. Here we provide evidence in AD brains of a specific up-regulation of an NF-kappaB-sensitive miRNA-146a highly complementary to the 3'-untranslated region of complement factor H (CFH), an important repressor of the inflammatory response of the brain. Up-regulation of miRNA-146a coupled to down-regulation of CFH was observed in AD brain and in interleukin-1beta, Abeta42, and/or oxidatively stressed human neural (HN) cells in primary culture. Transfection of HN cells using an NF-kappaB-containing pre-miRNA-146a promoter-luciferase reporter construct in stressed HN cells showed significant up-regulation of luciferase activity that paralleled decreases in CFH gene expression. Treatment of stressed HN cells with the NF-kappaB inhibitor pyrollidine dithiocarbamate or the resveratrol analog CAY10512 abrogated this response. Incubation of an antisense oligonucleotide to miRNA-146a (anti-miRNA-146a; AM-146a) was found to restore CFH expression levels. These data indicate that NF-kappaB-sensitive miRNA-146a-mediated modulation of CFH gene expression may in part regulate an inflammatory response in AD brain and in stressed HN cell models of AD and illustrate the potential for anti-miRNAs as an effective therapeutic strategy against pathogenic inflammatory signaling.

More news stories

Evaluating a new way to open clogged arteries

Over the past few decades, scientists have developed many devices that can reopen clogged arteries, including angioplasty balloons and metallic stents. While generally effective, each of these treatments ...

Making quantum encryption practical

One of the many promising applications of quantum mechanics in the information sciences is quantum key distribution (QKD), in which the counterintuitive behavior of quantum particles guarantees that no one can eavesdrop on ...