The new findings, published in the Frontiers in Aging Neuroscience, found a natural compound that may help reduce neurotoxicity in the Alzheimer’s brain.
Short-chain fatty acids (SCFAs) – metabolites produced by healthy gut bacteria and the primary source of nourishment for cells in your colon – may help to brain function, according to emerging data. SCFAs are frequently depleted in elderly adults with mild cognitive impairment and Alzheimer’s disease, the most prevalent type of dementia. However, the mechanism through which this drop in SCFAs contributes to the course of Alzheimer’s disease is still unknown.
SCFAs produced from the gut that travel to the brain via the bloodstream can bind to and activate the free fatty acid receptor 2 (FFAR2), a cell signaling protein expressed on neurons.
“Our study is the first to discover that stimulation of the FFAR2 sensing mechanism by these microbial metabolites (SCFAs) can be beneficial in protecting brain cells against toxic accumulation of the amyloid-beta (Aβ) protein associated with Alzheimer’s disease,” said Professor Hariom from the USF Health Morsani College of Medicine.
One of the two hallmark pathologies of Alzheimer’s disease is the formation of amyloid protein plaques in the brain due to hardened deposits of A clumping together between nerve cells. The other is tau protein neurofibrillary tangles within brain cells. These diseases contribute to cell loss and death, which eventually lead to the beginning of Alzheimer’s disease, a neurodegenerative disease marked by memory, thinking, and other cognitive abilities loss.
Dr. Yadav and his collaborators analyze molecular processes to better understand how interactions between the gut microbiome and the brain may affect brain health and age-related cognitive decline. According to Dr. Yadav, the purpose of this work was to elucidate the “previously unknown” role of FFAR2 in the brain.
The researchers first demonstrated that suppressing the FFAR2 receptor (by preventing it from sensing SCFAs in the environment outside the neuronal cell and transmitting signalling inside the cell) contributes to the aberrant development of the A protein associated with Alzheimer’s disease.
The researchers next conducted a large-scale virtual screening of over 144,000 active compounds in order to identify possible candidates that could imitate the positive effect of microbiota-produced SCFAs on FFAR2 signaling. It is critical to identify a natural chemical alternative to SCFAs that targets the FFAR2 receptor on neurons optimally, because the majority of these microbial metabolites are consumed by cells in the stomach and other organs before they reach the brain via blood circulation, Dr. Yadav stated.
Dr. Yadav’s team refined 15 potential compounds to the most powerful one. Fenchol, a plant-derived molecule responsible for the distinctive scent of basil, was the most effective at binding to the FFAR’s active region and stimulating signaling.
Additional tests in human neural cell cultures, Caenorhabditis (C.) elegans (worm), and mice models of Alzheimer’s disease indicated that fenchol dramatically reduced excess Aβ buildup and neuronal death by increasing FFAR2 signaling, the microbiota sensing system. When the researchers explored how fenchol controls Aβ-induced neurotoxicity in greater detail, they discovered that the molecule reduced the number of senescent neuronal cells, also known as “zombie” cells, which are frequently present in brains with Alzheimer’s disease pathology.
Zombie cells cease replication and die a slow death. Meanwhile, Dr. Yadav explained, they accumulate in diseased and ageing organs, create a detrimental inflammatory environment, and convey stress or death signals to surrounding healthy cells, which eventually mutate or die.
“Fenchol actually affects the two related mechanisms of senescence and proteolysis,” Dr. Yadav said of the intriguing preclinical study finding.
“It reduces the formation of half-dead zombie neuronal cells and also increases the degradation of (nonfunctioning) Aβ, so that amyloid protein is cleared from the brain much faster.”
Before you start adding extra basil to your spaghetti sauce or anything else you eat to help prevent dementia, additional research – including in humans – is required.
Image Credit: Getty
You were reading: A natural compound found in basil may help protect your brain from dementia