Researchers at Buck Institute have identified the role of insoluble proteins in aging and Alzheimer’s disease, uncovering their widespread presence beyond just amyloid and tau proteins. Their study in worms demonstrates that boosting mitochondrial health can reverse the detrimental effects of these protein aggregates, suggesting new treatment strategies for neurodegenerative diseases and aging by targeting mitochondrial health and overall protein insolubility. Insoluble protein aggregates accumulating in the brain are a recognized characteristic of Alzheimer’s disease and other neurodegenerative disorders.

Similarly, during normal disease-free aging, there is an accumulation of these insoluble proteins. To date, approaches to treatments for Alzheimer’s disease have not addressed the contribution of protein insolubility as a general phenomenon, instead focusing on one or two insoluble proteins. Buck researchers have recently completed a systematic study in worms that paints an intricate picture of the connections between insoluble proteins in neurodegenerative diseases and aging.

Furthermore, the work demonstrated an intervention that could reverse the toxic effects of the aggregates by boosting mitochondrial health. “Based on our discoveries, targeting insoluble proteins could provide a strategy for the prevention and treatment of a variety of age-related diseases,” said Edward Anderton, PhD, a postdoctoral fellow in Gordon Lithgow’s lab and co-first author of a s.