An analog that mimics mitochondrial protein called coenzyme Q10 (CoQ10) has been found to protect neuronal mitochondria from the damaging effects of protein aggregates seen in Alzheimer’s disease. The compound, developed by researchers at Arizona State University, may help researchers prevent the toxic effects of amyloid beta aggregates in the brain.
Poor functioning of small organelles known as mitochondria — the powerhouses of cells — is an early event in Alzheimer’s disease. Preclinical studies have shown that the accumulation of both amyloid beta and oligomeric amyloid beta, the small aggregates of amyloid protein commonly found in the brain with Alzheimer’s disease, were toxic to mitochondria. This suggests that these molecules may contribute to the metabolic deficits observed in Alzheimer’s disease, researchers wrote.
“Mitochondria are the major source of energy in brain cells, and deficiencies in energy metabolism have been shown to be one of the earliest events in Alzheimer’s disease pathobiology,” Diego Mastroeni, the study’s lead author and a scientist at the ASU-Banner Neurodegenerative Disease Research Center, said in a press release.
Researchers first isolated a type of neurons, called pyramidal cells, from the hippocampus of Alzheimer’s patients who had succumbed to the disease. They found that compared to cells from non-diseased controls, the pyramidal cells showed a marked decrease in expression of several mitochondrial genes.
A similar level of decrease also was detected in vitro when researchers exposed cells from a human neuroblastoma line (cancer cells from nerve tissue) to oligomeric amyloid beta, revealing the detrimental effects of oligomeric amyloid beta on the mitochondria of neurons.
The team then pretreated the human brain cells with a compound it designed to mimic the action of a natural component within mitochondria, CoQ10. CoQ10 protects and helps boost mitochondria energy production.
The results showed that pretreating the neuron cells with the CoQ10 analog protects the mitochondria from the effects of oligomeric amyloid beta, “providing an effective pretreatment option to prevent OAb toxicity,” they wrote.
“This study reinforces the toxicity of oligomeric amyloid beta on neuronal mitochondria and stresses the importance for protective compounds to protect the mitochondria from oligomeric amyloid beta toxicity,” Mastroeni said.
The team also noted that these findings offer “the opportunity for more precise (cell-type specific) elucidation of molecular events in Alzheimer’s disease that lead to mitochondrial dysfunction.”