PH imbalance in brain cells may lead to Alz’s

Study identifies potential drug targets to reverse problem

KUWAIT CITY, Aug 6, (Agencies): Johns Hopkins Medicine scientists say they have found new evidence in lab-grown mouse brain cells, called astrocytes, that one root of Alzheimer’s disease may be a simple imbalance in acid-alkaline — or pH — chemistry inside endosomes, the nutrient and chemical cargo shuttles in cells.

Astrocytes work to clear so-called amyloid beta proteins from the spaces between neurons, but decades of evidence has shown that if the clearing process goes awry, amyloid proteins pile up around neurons, leading to the characteristic amyloid plaques and nerve cell degeneration that are the hallmarks of memory-destroying Alzheimer’s disease.

The new study, described online June 26 in Proceedings of the National Academy of Sciences, also reports that the scientists gave drugs called histone deacetylase (HDAC) inhibitors to pHimbalanced mice cells engineered with a common Alzheimer’s gene variant. The experiment successfully reversed the pH problem and improved the capacity for amyloid beta clearance.

HDAC inhibitors are approved by the US Food and Drug Administration for use in people with certain types of blood cancers, but not in people with Alzheimer’s. They cautioned that most HDAC inhibitors cannot cross the blood-brain barrier, a significant challenge to the direct use of the drugs for brain disorders. The scientists say they are planning additional experiments to see if HDAC inhibitors have a similar effect in lab-grown astrocytes from Alzheimer’s patients, and that there is the potential to design HDAC inhibitors that can cross the barrier.

However, the scientists caution that even before those experiments can happen, far more research is needed to verify and explain the precise relationship between amyloid proteins and Alzheimer’s disease, which affects an estimated 50 million people worldwide. To date, there is no cure and no drugs that can predictably or demonstrably prevent or reverse Alzheimer’s disease symptoms.

“By the time Alzheimer’s disease is diagnosed, most of the neurological damage is done, and it’s likely too late to reverse the disease’s progression,” says Rajini Rao, PhD, professor of physiology at the Johns Hopkins University School of Medicine. “That’s why we need to focus on the earliest pathological symptoms or markers of Alzheimer’s disease, and we know that the biology and chemistry of endosomes is an important factor long before cognitive decline sets in.”

Nearly 20 years ago, scientists at Johns Hopkins and New York University discovered that endosomes, circular compartments that ferry cargo within cells, are larger and far more abundant in brain cells of people destined to develop Alzheimer’s disease. This hinted at an underlying problem with endosomes that could lead to an accumulation of amyloid protein in spaces around neurons, says Rao.

Vaccinations against a new outbreak of Ebola virus in eastern Democratic Republic of Congo are due to begin on Wednesday, a senior official at the health ministry said on Sunday.

The experimental vaccine, which is manufactured by Merck , proved successful during its first wide-scale usage against an outbreak in northwestern Congo that was declared over less than two weeks ago.

More than 3,000 doses remain in stock in the capital Kinshasa, allowing authorities to quickly deploy it to the affected areas near the Ugandan border.

As with the previous outbreak, vaccination will focus on health workers and people who have come into contact with confirmed cases of the disease, said Barthe Ndjoloko, who oversees the health ministry’s Ebola response.

PARIS:

Also:

Vietnam has reported three outbreaks of highly pathogenic H5N6 bird flu among backyard birds, the Paris-based World Organisation for Animal Health (OIE) said on Friday, citing a report from the Vietnamese farm ministry.

The first outbreak was detected on July 28 in a backyard flock of 2,400 birds in the province of Nghe An. It directly killed 90 birds.

On the same day, it was detected in the province of Hai Phong in a flock of 4,720 birds, where it killed 500 birds.

And on July 30 the virus was detected in another backyard in Hai Phong with 5,500 birds where it had killed 1,000 of them.

Birds that were not killed have been slaughtered, it said.

The types of birds were not indicated and the source of the disease not known.