New study shows that two experimental drugs can reverse age-related cognitive impairment and potentially treat Alzheimer’s disease, by restoring mitochondrial function in the aging brain.
Dementia and Alzheimer’s disease, in particular, are the most common neurodegenerative disorders associated with aging. Although aging is the most important risk factor for the development of Alzheimer’s disease, certain genes, family history, abnormal protein deposits in the brain, and environmental factors are also known to contribute to the development of this disorder. However, the role of mitochondria in Alzheimer’s disease is unclear [1,2].
Alzheimer’s disease results from the progressive death of nerve cells in the brain. This brain cell loss leads to several symptoms and pathological behaviours characterising Alzheimer’s disease, including memory loss, problems with language, confusion, as well as personality and behaviour changes. Even though cases of early-onset do exist, most people diagnosed with Alzheimer’s disease are older than 65. However, how aging promotes Alzheimer’s disease is not entirely understood [1,2] – but that might be about to change:
Antonio Currais and his colleagues from the Salk Institute for Biological Studies and the Scripps Research Institute, California, aimed at identifying drugs to target age-associated neurodegeneration. Their efforts led to the identification of two natural compounds -CMS121 and J147- that prevented cognitive impairment and other aspects of aging in mouse models of Alzheimer’s disease. Interestingly, they found that mice treated with these two compounds continued to express genes involved in the maintenance of mitochondrial function throughout aging.
They also found that the neuroprotective effects of these two drugs are mediated through increasing the levels of a chemical called acetyl-coenzyme A and enhancing histone acetylation in neurons, which helped to maintain the mitochondrial function and energy production, preventing the molecular changes that are associated with aging. The findings of this study were published in eLife .
In the study  the team commented: “Because the current approach to AD [Alzheimer’s disease] drug discovery has largely failed, we devised a novel drug discovery paradigm based on phenotypic screening assays that mimic numerous aspects of old age-associated neurodegeneration and brain pathology, including energy failure and mitochondrial dysfunction.”
Mitochondrial dysfunction has emerged as a hallmark of both normal aging and Alzheimer’s disease. This study provided functional evidence on the neuroprotective roles of mitochondria and metabolism in the aging brain and identified potential molecular targets to treat dementia. However, the role of mitochondrial dysfunction in aging or Alzheimer’s disease, and whether targeting mitochondrial dysfunction can reverse age-related cognitive impairment, need to be further investigated in human studies.