Eugenia Trushina

Abstract:

A decreased ability to maintain consistent energy production and a low level of oxidative stress in brain cells have been identified among the underlying factors for the development of various neurodegenerative conditions, such as Alzheimer's disease (AD). Mitochondria play a central role in maintaining energy homeostasis and generating reactive oxygen species in cells. Mitochondrial dysfunction is well documented in AD patients.  However, recent evidence has revealed the important roles of mitochondria signaling in adapting to energy stress, promoting survival and function, and restoring energy levels. Mitochondria signaling coordinates several crucial cellular mechanisms, including maintaining energy balance, metabolic functions, autophagy, epigenetic modifications, regulating inflammation, providing antioxidant protection, and regulating cell death. Thus, harnessing mitochondrial signaling could represent a novel therapeutic strategy to improve and maintain multiple essential mechanisms of cell survival. We have developed small molecules that target mitochondria and mildly reduce the activity of mitochondrial complex I, resulting in the induction of mild energetic stress. This approach has proven effective in delaying the onset of AD in multiple transgenic mouse models and promoting healthy aging in wild-type mice [1-6]. The mechanism of action involves activating various neuroprotective mechanisms involved in adaptive stress response, which ultimately results in promoting health and longevity, and restoring mitochondria function and energy balance in the brain.