Research Roundup: New Insights into Alzheimer’s Disease and More
Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.
Unusual Molecular Chaperone Implicated in Alzheimer’s Disease
Two specific abnormal proteins accumulate in the brains of Alzheimer’s patients. The first is beta amyloid and the second is tau. Generally, accumulations of beta amyloid occur earlier in the disease and tau later in the disease. Tau accumulates in the form of fibers and disrupts nerve cell communication. Until now, researchers didn’t know much about this tau formation. Researchers at the University of Kostanz (Germany) and Utrecht University (Netherlands) utilized structural analyses to better understand the biochemical mechanism of a molecular chaperone, or helper protein, that plays an unexpected role in tau formation. They published their research in the journal Science Advances.
Tau does not have a clearly defined structure. “We can imagine it like a rope: it can be sometimes elongated, sometimes bent, sometimes looped,” said Malte Drescher, a chemist at Konstanz who led the research.
Typically, tau has a recurved structure, something like a paper clip. But when the chaperone Heat Shock Protein 90 (HSP-90) encounters tau, the chaperone causes tau’s paper clip shape to open.
“The area in the middle of the paper clip is thus exposed and made accessible,” said Sabrina Weickert, lead author of the study. Weickert is a biophysicist and doctoral researcher in Drescher’s laboratory. “The area is known to be responsible for aggregation, i.e. for attachment of further tau proteins to the molecule.”
This unfolded form allows tau molecules to be stacked on top of each other, known as oligomerization.
“This oligomerization by HSP-90 came as a big surprise,” said Drescher. “A chaperone is actually responsible for exactly the opposite: It is supposed to bring a protein into a defined form and under no circumstances contribute to the formation of a ‘protein pile.’”
It's not clear if the chaperone involvement and resulting structure is what causes Alzheimer’s or is the body’s response, but answering that question and others will be the key to further research.
More than 10% of Coronavirus Victims Infected by Someone with No Symptoms
Investigators at University of Texas at Austin studying the novel coronavirus that causes COVID-19 found that the virus is very infectious, with the time between cases in a chain of transmission less than a week, and that more than 10% of patients are infected by somebody who has the virus but doesn’t have symptoms. The average serial interval was about four days. This is very similar to the flu, but it also means it is more difficult to contain.
Halting Blood Vessel Formation to Stop Tumor Growth
Angiogenesis is the formation of new blood vessels that tumors use to grow. For some time, it was thought that by interfering with that process, it would be an effective cancer treatment, but it hasn’t lived up to its promise because tumor cells produce more stimulatory molecules in response. National Institute of Health (NIH) researchers attempted a new strategy that halted angiogenesis by blocking any of the enzymes in what is knock as the PIP2 recycling series. In mice, it led to less tumor and tumor blood vessel growth.
Disengaging from Difficult Tasks and Goals After Retirement Associated with Cognitive Decline
Some middle-aged and older adults, after retirement, tend to disengage from difficult tasks or goals. A new study associates this with a greater risk of cognitive decline. It analyzed 7,108 participants in the Midlife in the United States national longitudinal study, especially a subset of 732 participants. Half were female and 94% were white. Earlier research has associated retirement with higher risk of cognition problems, although there could be many factors, including simply aging, to reinforce that. However, this research measured participants’ level of goal disengagement and found that people who didn’t set goals and embraced that premise were more prone to cognitive problems.
Potential Drug to Prevent Spread of Coronavirus that Causes COVID-19
Infection researchers at the German Primate Center have identified a cellular enzyme called TMPRSS2, that viruses require to enter lung cells. They have identified a clinically-proven drug that is active against TMPRSS2 that blocks SARS-CoV-2 infection and has the potential as a novel treatment against COVID-19. The research included scientists from Charite, the University of Veterinary Medicine Hannover Foundation, the BG Unfallklilnik Murnau, the LMU Munich, the Robert Koch Institute and the Germany Center for Infection Research.
The drug camostat mesylate inhibits TMPRSS2.
“We have tested SARS-CoV-2 isolated from a patient and found that camostat mesylate blocks entry of the virus into lung cells,” said Markus Hoffmann, lead author of the study. The drug is approved in Japan for pancreatic inflammation. “Our results suggest that camostat mesylate might also protect against COVID-19. This should be investigated in clinical trials.”
Researchers ID Protein that Controls Inflammation
Inflammatory diseases include rheumatoid arthritis, Crohn’s disease and psoriasis, but inflammation has also been implicated in numerous other diseases, including cardiovascular disease, cancer, and Alzheimer’s disease. Researchers discovered how a protein called A20 prevents inflammation and autoimmunity. Unexpectedly, it was not via the protein’s enzymatic activities, but through a non-enzymatic mechanism, which opens up possibilities for new approaches to therapies. The anti-inflammatory activity of A20 relies on a specific domain within the protein that can bind to ubiquitin, a modification found on other proteins. This lets A20 interfere with signaling pathways inside the cell and prevents the activation of cellular responses that would otherwise cause inflammation and disease development.
Diarrhea Prominent Symptom of COVID-19
Although early reports about COVID-19, the disease caused by the novel coronavirus, suggested that diarrhea was not a common symptom, a new study published in The American Journal of Gastroenterology, said it was. COVID-19 is typically a sere case of viral pneumonia that can be life-threatening. The research came out of a cross-sectional multicenter study from China by investigators from the Wuhan Mediacl Treatment Expert Group for COVID-19.
The authors wrote, “Clinicians must bear in mind that digestive symptoms, such as diarrhea, may be a presenting feature of COVIDI-19, and that the index of suspicion may need to be raised earlier in these cases rather than waiting for respiratory symptoms to emerge.”