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Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease.

ABSTRACT: Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

SUBMITTER: Horowitz AM

PROVIDER: S-EPMC5539850 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Fundamental organelles that occur in every cell type with the exception of mammal erythrocytes, the mitochondria are required for multiple pivotal processes that include the production of biological energy, the biosynthesis of reactive oxygen species, the control of calcium homeostasis, and the triggering of cell death. The disruption of anyone of these processes has been shown to impact strongly the function of all cells, but especially of neurons. In this review, we discuss the role of the mitochondria impairment in the development of the neurodegenerative diseases Amyotrophic Lateral Sclerosis, Parkinson's disease and Alzheimer's disease. We highlight how mitochondria disruption revolves around the processes that underlie the mitochondria's life cycle: fusion, fission, production of reactive oxygen species and energy failure. Both genetic and sporadic forms of neurodegenerative diseases are unavoidably accompanied with and often caused by the dysfunction in one or more of the key mitochondrial processes. Therefore, in order to get in depth insights into their health status in neurodegenerative diseases, we need to focus into innovative strategies aimed at characterizing the various mitochondrial processes. Current techniques include Mitostress, Mitotracker, transmission electron microscopy, oxidative stress assays along with expression measurement of the proteins that maintain the mitochondrial health. We will also discuss a panel of approaches aimed at mitigating the mitochondrial dysfunction. These include canonical drugs, natural compounds, supplements, lifestyle interventions and innovative approaches as mitochondria transplantation and gene therapy. In conclusion, because mitochondria are fundamental organelles necessary for virtually all the cell functions and are severely impaired in neurodegenerative diseases, it is critical to develop novel methods to measure the mitochondrial state, and novel therapeutic strategies aimed at improving their health.

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Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease.

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