Research Roundup: A Potential Cause of Alzheimer’s Disease and More

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Research Roundup: A Potential Cause of Alzheimer’s Disease and More

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

A Potential Cause of Alzheimer’s Disease

Alzheimer’s disease is associated with an abnormal accumulation of two proteins — beta-amyloid and tau. However, about 20% of people have the plaques (amyloid) but no signs of dementia. Researchers at University of California, Riverside conducted research into tau to determine if they could discover more about the mechanism behind the neurofibrillary tangles caused by tau. They focused on different structures a single molecule can take, called isomers. Ryan Julian, a UCR professor of chemistry, said, “An isomer is the same molecule with a different three-dimensional orientation than the original. A common example would be hands. Hands are isomers of each other, mirror images but not exact copies. Isomers can actually have a handedness.”

In their research, published in the Journal of Proteome Research, Julian and his team scanned all the proteins in brain samples that had been donated. In the brains where there was an accumulation of tau but no diagnoses of dementia, they found normal tau had a different-handed form than in patients who developed plaques or tangles and dementia. They also found that the proteins survived longer than was typical. The majority of proteins in the body have a half-life of less than 48 hours. But if a protein remains too long, some amino acids in the proteins convert into the “other-handed” isomer. Most normal proteins in living things are left-handed.

Source: BioSpace

Julian notes, “If you try to put a right-handed glove on your left hand, it doesn’t work too well. It’s a similar problem in biology; molecules don’t work the way they’re supposed to after a while because a left-handed glove can actually convert into a right-handed glove that doesn’t fit.”

Although uncertain, they speculate that the reason these “other-handed” isomers accumulate is related to a defect in the individual’s ability to clear defective proteins, called autophagy.

Deleting Dysfunctional Fat Cells Alleviates Diabetes

Researchers with the University of Connecticut found that using a combination of experimental drugs, dasatinib and quercetin, in mice models for diabetes, could alleviate symptoms of the disease. The drugs help clear away senescent fat cells. The tissue was donated by obese individuals with known metabolic problems. Without treatment, the human fat tissues created metabolic problems in immune-deficient mice. But after being treated with the two drugs, the harmful metabolic effects were almost completely eliminated. In earlier studies, the two drugs demonstrated the ability to extend lifespan and good health in elderly mice.

Repurposed ALS Drug Looks Promising in Niemann-Pick Disease Type C1

Investigators with the National Institutes of Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health and Human Development found that a drug used to treat amyotrophic lateral sclerosis (ALS) appears to slow the loss of a specialized brain cell in Niemann-Pick disease type C1 (NPC1). NPC1 is a rare genetic disorder that affects children and adolescents. The drug is riluzole. NPC1 is caused by an impaired ability to transport cholesterol through cells. This leads to problems controlling movement, liver and lung disease, problems swallowing, intellectual decline and death. Most of the movement problems came from loss of Purkinje neurons in the brain. They found that mice with a type of NPC1 have a decreased ability to lower levels of glutamate after it’s bound to a neuron’s surface. Glutamate is a brain chemical that stimulates neurons. The research team theorizes the glutamate accumulation contributes to the loss of Purkinje cells. Riluzole blocks the release of glutamate and delays ALS progression.

New Potential Therapeutic Pathway for Chronic Viral Infections

Scientists with Monash University found that during chronic viral infections, a protein dubbed BMI-1 is switched on too early in B cells. This results in an unbalance in gene expression, causing antibodies to be less effective in clearing the viruses. The study was in mice. They found that when they targeted the protein, the B cells appeared to manufacture higher quality antibodies that cleared viruses better. They believe this could be a new therapeutic pathway for regulating the body’s antibody response to infections. The so-called “low-quality” B cells are plasma cells, which are activated quickly after infection and produce antibodies fast but are not considered high quality and don’t clear the infection. But this activity gives the immune system time for other B cells to undergo a “training period” where they become “high-quality” memory B cells and plasma cells for immunity. Memory B cells maintain immune memory for a long time, and if they encounter the same pathogen, quickly become plasma cells and churn out high-quality antibodies that are already able to attack the germs without the training period.

Experimental Lyme Disease Vaccine Shows Promise

Researchers at Yale University have developed a vaccine against Lyme disease that, in guinea pigs at least, offers protection against infection. It may also fight other tick-borne diseases. The vaccine doesn’t specifically train the immune system against the bacterium that causes Lyme disease, but instead targets components of tick saliva. This is an mRNA vaccine similar to those developed against COVID-19 by Moderna and Pfizer-BioNTech. The vaccine is designed to attack proteins in the saliva of black-legged tick Ixodes scapularis, which transmits the Lyme disease bacteria, Borrelia burgdorferi. The researchers focused on 19 individual proteins.

“There are multiple tick-borne diseases, and this approach potentially offers more broad-based protection than a vaccine that targets a specific pathogen,” said senior author Erol Fikrig, the Waldemar Von Zedtwitz Professor of Medicine (Infectious Diseases) at Yale and professor of epidemiology (microbial diseases and of microbial pathogenesis. “It could also be used in conjunction with more traditional, pathogen-based vaccines to increase their efficacy.”

One problem noted so far, however, is that the vaccine did not seem to work in mice. Mice can’t acquire natural tick resistance after an infection and are natural reservoirs for I. scapularis ticks. There may be other potential factors, such as the skin — guinea pig skin is similar to human skin in the number of layers.

BioSpace source:

https://www.biospace.com/article/research-roundup-a-potential-cause-of-alzheimer-s-disease-and-more