Alzheimer's Disease: From Mitochondrial Perturbations to Mitochondrial Medicine.
Age-related neurodegenerative diseases such as Alzheimer's disease (AD) are distressing conditions causing countless levels of suffering for which treatment is often insufficient or inexistent. Considered to be the most common cause of dementia and an incurable, progressive neurodegenerative disorder, the intricate pathogenic mechanisms of AD continue to be revealed and, consequently, an effective treatment needs to be developed. Among the diverse hypothesis that have been proposed to explain AD pathogenesis, the one concerning mitochondrial dysfunction has raised as one of the most discussed with an actual acceptance in the field. It posits that manipulating mitochondrial function and understanding the deficits that result in mitochondrial injury may help to control and/or limit the development of AD. To achieve such goal, the concept of mitochondrial medicine places itself as a promising gathering of strategies to directly manage the major insidious disturbances of mitochondrial homeostasis as well as attempts to directly or indirectly manage its consequences in the context of AD. The aim of this review is to summarize the evolution that occurred from the establishment of mitochondrial homeostasis perturbation as masterpieces in AD pathogenesis up until the development of mitochondrial medicine. Following a brief glimpse in the past and current hypothesis regarding the triad of aging, mitochondria and AD, this manuscript will address the major mechanisms currently believed to participate in above mentioned events. Both pharmacological and lifestyle interventions will also be reviewed as AD-related mitochondrial therapeutics.
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Susana
S
Cardoso
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Cristina
C
Carvalho
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Institute for Interdisciplinary Research, University of Coimbra, Coimbra, Portugal.
Sónia C
SC
Correia
Laboratory of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.|IBILI-Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Raquel M
RM
Seiça
CNC-Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.|Laboratory of Physiology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Paula I
PI
Moreira
D000375:Aging; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001343:Autophagy / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects; D000070497:Healthy Lifestyle; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D028361:Mitochondrial Diseases / Q000378:metabolism / Q000628:therapy*; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants
Alzheimer's disease; mitochondrial anomalies; mitochondrial targets