Reprinted with the kind permission of Life Extension.
December 8 2017. An article appearing on December 6, 2017 in Nature reports that improving mitochondrial defenses reduces the formation of amyloid plaques that are characteristic of Alzheimer’s disease. Mitochondria, the cells’ power plants, produce energy used by the body and brain. Unprotected mitochondria could increase the brain’s susceptibility to damage and the development of Alzheimer’s disease.
“Here we provide bioinformatic and experimental evidence of a conserved mitochondrial stress response signature present in diseases involving amyloid-beta proteotoxicity in human, mouse and Caenorhabditis elegans that involves the mitochondrial unfolded protein response and mitophagy pathways,” write Vincenzo Sorrentino and colleagues. “Using a worm model of amyloid-beta proteotoxicity, GMC101, we recapitulated mitochondrial features and confirmed that the induction of this mitochondrial stress response was essential for the maintenance of mitochondrial proteostasis and health.”
“These defense and recycle pathways of the mitochondria are essential in organisms, from the worm C. elegans all the way to humans,” Dr Sorrentino explained. “So, we decided to pharmacologically activate them.”
The researchers evaluated the antibiotic doxycycline and the vitamin nicotinamide riboside (NR), which can activate the mitochondrial unfolded protein response and mitophagy defense systems in a worm model of Alzheimer’s disease. They observed improved health, performance and lifespan, and less amyloid plaque when the compounds were administered to the worms in comparison with untreated worms. Benefits were also found in human neuronal cells. When NR was tested in a mouse model of Alzheimer’s disease, mitochondrial and cognitive function improved, and plaque formation was reduced.
“So far, Alzheimer’s disease has been considered to be mostly the consequence of the accumulation of amyloid plaques in the brain,” senior author Johan Auwerx stated. “We have shown that restoring mitochondrial health reduces plaque formation – but, above all, it also improves brain function, which is the ultimate objective of all Alzheimer’s researchers and patients.”
“By targeting mitochondria, nicotinamide riboside and other molecules that stimulate their ‘defense and recycle’ systems could perhaps succeed where so many drugs, most of which aim to decrease amyloid plaque formation, have failed,” Dr Sorrentino added.