Abstract
Neurodegenerative diseases are intricate in nature because of the involvement of the multiple pathophysiological events including mitochondrial dysfunction, neuroinflammation and oxidative stress. Alzheimer’s disease (AD) is a neurodegenerative disease explained by extracellular amyloid β deposits, intracellular neurofibrillary tangles and mitochondrial dysfunction. Increasing evidence has indicated that mitochondrial dysfunction displays significant role in the pathophysiological processes of AD. Mitochondrial dysfunction involves alterations in mitochondrial respiratory enzyme complex activities, oxidative stress, opening of permeability transition pore, and enhanced apoptosis. Various bioenergetics and antioxidants have been tried or under different investigational phase against AD and other neurodegenerative disorders (Parkinson’s disease, Huntington’s disease, and Amyotrophic lateral sclerosis) because of their complex and multiple site of action. These mitochondrial-targeting bioenergetics and antioxidant compounds such as coenzyme Q10, idebenone, creatine, mitoQ, mitovitE, MitoTEMPOL, latrepirdine, methylene blue, triterpenoids, SS peptides, curcumin, Ginkgo biloba, and omega-3 polyunsaturated fatty acids with potential efficacy in AD have been identified. Present review is intent to discuss mitochondrial restorative mechanisms of these bioenergetics and antioxidants as a potential alternative drug strategy for effective management of AD.
Highlights
Alzheimer’s disease (AD) common incapacitating neurodegenerative disease, identified by the occurrence of senile plaques extracellularly and neurofibrillary tangles intracellularly (Alzheimer’s, 2015; Kumar et al, 2015)
Preclinical Studies A study showed that SS peptides decrease mitochondrial reactive oxygen species (ROS) generation, inhibit mitochondrial swelling, and reduce cytochrome c release from mitochondria in different experimental models (Szeto, 2008). These findings have suggested their therapeutic potential in neurodegenerative disorders including AD
Previous evidences have shown the potential efficacy of various bioenergetics and antioxidants having in the treatment of AD, for example coenzyme Q10, carnitine, α-lipoic acid, Idebenone, mito-targeted compounds like Mito Q, Mito Vit E and Mito TEMPOL, Ginkgo biloba, curcumin and omega-3 polyunsaturated fatty acids
Summary
Alzheimer’s disease (AD) common incapacitating neurodegenerative disease, identified by the occurrence of senile plaques extracellularly and neurofibrillary tangles intracellularly (Alzheimer’s, 2015; Kumar et al, 2015). Strong evidence indicated that mitochondrial dysfunction involves alterations of mitochondrial respiratory chain enzymes, generation of reactive oxygen species (ROS), opening of mitochondrial permeability transition pore (mPTP), structural abnormalities of mitochondria, oxidative stress and apoptosis (Hauptmann et al, 2006; Lin and Beal, 2006; Eckert and Müller, 2014) These mitochondrial abnormalities are known to occur early in AD before Aβ deposition and are closely related to Aβ- or tau- pathology (Swerdlow et al, 2010; Maruszak and Żekanowski, 2011). An attempt has been made to discuss various compounds targeting mitochondria and oxidative stress as a future approach with major focus on AD pathology
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