Researchers from The Buck Institute for Research in Novato, CA, have proposed that there are other proteins in brain clumps associated with Alzheimer’s disease that have been overlooked but could play a role in the development of the disease. Their study found that the accumulation of insoluble proteins, induced by both the natural aging process and beta-amyloid, could potentially accelerate Alzheimer’s disease. Using a worm model, the researchers boosted the quality of mitochondrial health in insoluble proteins, which helped delay the toxic effects of beta-amyloid. This research sheds light on protein clumping in Alzheimer’s disease and the potential role of mitochondrial health in combating the disease.
The accumulation of protein clumps, particularly beta-amyloid and tau, in the brain is known to characterize Alzheimer’s disease. However, researchers like Edward Anderton from The Buck Institute for Research on Aging have suggested that there are hundreds of additional proteins in these brain clumps that have been neglected until now. By studying the insoluble proteins in these clumps, researchers found that beta-amyloid drives other proteins to become insoluble, potentially contributing to the progression of Alzheimer’s disease. The team utilized a compound to improve mitochondrial health in insoluble proteins, showing promise for delaying the toxic effects of beta-amyloid and potentially halting the disease’s progression.
Proteins are essential elements of cells that need to maintain their specific shape to function correctly. When proteins lose their shape due to factors like stress, aging, or damage, they can form insoluble protein aggregates. Research scientist Manish Chamoli explained that as organisms age, they tend to accumulate these insoluble proteins, which has also been observed in conditions like Alzheimer’s disease. By studying the connections between brain protein clumping in normal aging and the development of Alzheimer’s disease, researchers have identified how beta-amyloid influences the insolubility of proteins in a destructive feedforward cycle, accelerating the disease’s progression.
To counteract the negative effects of beta-amyloid on protein insolubility, researchers investigated ways to boost mitochondrial protein quality, as many mitochondrial proteins become insoluble with age and beta-amyloid influence. By targeting the electron transport chain in mitochondria with the compound urolithin A, researchers were able to reverse some of beta-amyloid’s harmful effects on protein insolubility. The study’s findings suggest that improving mitochondrial health could mitigate the negative effects of beta-amyloid toxicity, opening up potential interventions like pharmacological approaches, nutritional supplements, and lifestyle modifications for Alzheimer’s disease patients.
Dr. Verna R. Porter, a neurologist specializing in dementia and Alzheimer’s disease, noted that targeting mitochondrial health to address protein insolubility caused by beta-amyloid could offer a novel approach in Alzheimer’s disease treatment. She highlighted the importance of conducting clinical trials to test the efficacy of mitochondrial health-boosting compounds, such as urolithin A, in Alzheimer’s disease patients. By further exploring how beta-amyloid disrupts mitochondrial function and leads to protein insolubility, researchers may identify additional therapeutic targets for the disease. These findings have significant implications for potential interventions to combat Alzheimer’s disease and improve the quality of life for affected individuals.
