HOUSTON – A worrying new study shows a link between a common fungus and Alzheimer’s disease. Scientists at Baylor College of Medicine are revealing how the fungus Candida albicans it enters the brain, activates mechanisms that aid its elimination, and generates toxic protein fragments known as amyloid beta-like peptides (Ab), a key player in the development of Alzheimer’s disease.
“Our lab has years of experience studying fungi, so we set out to study the connection between them C. albicans i Alzheimer’s disease in animal models,” says the study’s corresponding author, Dr. David Corry, the Fulbright Endowed Chair in Pathology and professor of pathology and immunology and medicine at Baylor, in a university premiere. “In 2019 we reported it C. albicans it reaches the brain where it produces changes very similar to those seen in Alzheimer’s disease. The current study extends this work to understand the molecular mechanisms.”
The study first sought to find out how Candida albicans access the brain. The researchers discovered that the fungus produces enzymes called secreted aspartic proteases (Saps), which break down the blood-brain barrier, a protective barrier that normally prevents harmful substances from entering the brain. entering the brain. This gap allows the fungus to infiltrate the brain and cause damage.
The next question posed by the researchers was how the brain effectively clears the fungus. Previous research has shown this C. albicans brain infections are completely resolved in healthy mice after 10 days. In this study, the team revealed two mechanisms triggered by the fungus microglia brain cellswhich play a crucial role in the brain’s immune response.
“The same Saps that the fungus uses to breach the blood-brain barrier also break down the amyloid precursor protein into Ab-like peptides,” says the study’s first author, Dr. Yifan Wu, a pediatric postdoctoral scientist who works at the Corry laboratory. “These peptides activate microglial brain cells via a cell surface receptor called Toll-like receptor 4, which keeps the fungal load low in the brain, but does not clear the infection.”
Besides, C. albicans it produces a protein called candidalysin that binds to microglia via a different receptor, CD11b.
“Candidalysis-mediated activation of microglia is essential to clear it candidate in the brain,” notes Dr. Wu. “If we remove this pathway, the fungi are no longer effective erased in the brain.”
The implications of this research extend to understanding the development of Alzheimer’s disease. The prevailing theory suggests that Alzheimer’s is primarily due to the accumulation of toxic Ab-like peptides in the brain, leading to neurodegeneration. These peptides are believed to be produced endogenously within the brain.
However, the current study reveals an alternative source for these Ab-like peptides: C. albicans. This common fungus, previously detected in the brains of individuals with Alzheimer’s disease and other chronic neurodegenerative disorders, possesses its own set of proteases that can generate the same Ab-like peptides produced within the brain itself.
“We propose that the brain Ab peptide aggregates that characterize multiple Candida-associated neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease and others, can be generated both intrinsically by the brain and by C. albicans”, explains Dr. Corry. “These findings in animal models support the conduct of additional studies to evaluate the role of C. albicans in the development of Alzheimer’s disease in humans, which can potentially lead to innovative therapeutic strategies.”
The study is published in the journal Cell reports.
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