Losing the tail to survive. In neurons, the lizard’s strategy, losing the axon to be safe, could prevent cell death. Scientists at Harvard Medical School have observed that certain toxins activated axon loss to prevent damage and survive. This mechanism was mediated by the Gasdermin-E (GSDME) protein, which destroyed the mitochondria in the axons and eliminated the affected nerve projection before the cell died. The inhibition of GSDME prevented the loss of neurons and delayed the progression of amyotrophic lateral sclerosis (ALS) in mice models.
Two molecules that affected the cell cycle only of acute myeloid leukemia (AML) cells could be used as a clinical strategy against this pathology. Scientists at Memorial Sloan Kettering Cancer Center and Harvard University have discovered that DEG-35 and DEG-77 arrested the cell cycle and promoted cell differentiation and apoptosis in these cells.
A deficiency in fumarate metabolism could be behind a new mechanism of inflammation mediated by mitochondrial DNA and RNA. Two independent and simultaneous studies described how the accumulation of fumarate in the mitochondria released the genetic material of this organelle through vesicles, activating an inflammatory signaling pathway.
Scientists from Washington University in St. Louis have described a role for T cells in the neurodegeneration associated with the tau protein. Tau accumulation in the brain activated microglia. This signal triggered the activation of T cells in other parts of the body, attracting them to the brain. Once there, the interaction of these T cells and microglia produced the neuronal damage seen in Alzheimer’s disease and other tauopathies.
Autoantibodies are typically not good news. But a group of researchers from Bellinzona, Switzerland, have observed that the presence of autoantibodies against chemokines, a special class of cytokines, is associated with mild disease and less risk of developing long COVID. “Our hypothesis was that antibodies to chemokines, if they existed, would also be associated with a negative outcome of the disease. But, what we found, in fact, was the exact opposite of what we were predicting,” Davide Robbiani, director of the Institute for Research in Biomedicine, told BioWorld.
Bacteria inflaming the meninges have developed an immunosuppressive mechanism that contributes to their ability to attack the brain. Researchers found that, by activating pain receptors (nociceptors) to release chemical substances that block an immune cell receptor, Streptococcus pneumoniae and Streptococcus agalactiae deactivated the protective function of macrophages and weakened brain defenses. This, in turn, enabled them to invade the brain.
Scientists at the University of Virginia have discovered an anti-aging mechanism mediated by an enzyme that metabolizes alcohol. Alcohol dehydrogenase, which in Caenorhabditis elegans and yeast replaces the rejuvenating effect of autophagy, would reduce age-associated glycerol levels, also promoting longevity in mice and humans.
The intestinal microbiota could protect against HIV infection. At the 30th Conference on Retroviruses and Opportunistic Infections (CROI) last week, a group of scientists from Duke University presented data showing a preventive effect of two bacteria from the Lachnospiraceae family, the species Clostridium immunis and Ruminococcus gnavus against HIV. These microorganisms strongly inhibited HIV replication in vitro through the metabolic pathway of tryptophan and the aryl hydrocarbon receptor.
HIV research is a winding road where one obstacle leads to another, slowing down success. The first barrier to getting the cure starts before one can even talk about it. “Cure may be too powerful and promising a term. Remission is probably better,” said John Mellors, whose work led to the universal use of plasma HIV-1 RNA and CD4+ T-cell counts in HIV-1 infection.
“Cure means maintaining an undetectable viral load off antiretroviral treatment. That means you cannot transmit it to people. Within that definition, there are people that have complete eradication of every single virus. And then, you have people that have a low level of virus that are able to keep under control without drugs,” Sharon Lewin told BioWorld. “Remission is maintaining a viral load less than 50 copies per milliliter in the absence of any retroviral. But there is still virus detectable,” she explained. Lewin is the director of The Peter Doherty Institute for Infection and Immunity in Melbourne, and the president of the International AIDS Society (IAS).
Anthony Fauci has retired from his position as director of the National Institute of Allergy and Infectious Diseases (NIAID) and as chief medical advisor to the U.S. president. But Fauci, who has advised every president since Ronald Reagan, continues to share his encyclopedic knowledge with the HIV research community, as he has since the beginning of the HIV pandemic. Fauci co-founded the first National Conference on Human Retroviruses and related infections in 1993. At the Opening Session of the 30th edition of the Conference on Retroviruses and Opportunistic Infections (CROI), he highlighted the advances that have collectively extended the life expectancy of newly diagnosed patients by decades.
