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A review on mitochondrial restorative mechanism of antioxidants in Alzheimer's disease and other neurological conditions.

Kumar A, Singh A - Front Pharmacol (2015)

Bottom Line: Increasing evidence has indicated that mitochondrial dysfunction displays significant role in the pathophysiological processes of AD.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University , Chandigarh, India.

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.

No MeSH data available.


Related in: MedlinePlus

Role of mitochondria in AD. In early-onset AD, it is hypothesized that mitochondria leads to the generation of free radicals (, H2O2), which in turn decrease cytochrome oxidase activity and inhibit cellular ATP generation. Further in late-onset AD, free generation actives BACE mediated cleavage of Aβ. Again Aβ enter into the mitochondria and induces free radicals that leads to disruptions of ETC, decrease in cytochrome oxidase activity and the inhibition of ATP which finally leads to neuronal damage and cognitive decline in AD.
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Figure 2: Role of mitochondria in AD. In early-onset AD, it is hypothesized that mitochondria leads to the generation of free radicals (, H2O2), which in turn decrease cytochrome oxidase activity and inhibit cellular ATP generation. Further in late-onset AD, free generation actives BACE mediated cleavage of Aβ. Again Aβ enter into the mitochondria and induces free radicals that leads to disruptions of ETC, decrease in cytochrome oxidase activity and the inhibition of ATP which finally leads to neuronal damage and cognitive decline in AD.

Mentions: It is well documented that reduced cytochrome oxidase activity is correlated with an increased defects in mtDNA in AD (Swerdlow et al., 2014). The brain, due to the presence of high lipid content, high oxygen consumption and low antioxidant defenses, remains the most vulnerable organ to oxidative stress. It is also well documented that free radical generation by mitochondrial dysfunction affect both in neurons and astrocytes during AD. There is also generation of free radicals () produced in mitochondrial ETC complexes I and III and enzymes of the TCA (α-ketoglutarate dehydrogenase) in AD. From inner mitochondrial membranes hydrogen peroxide (H2O2) and is released to the outer side (cytoplasm) which finally causes oxidation of cytoplasmic proteins (Figure 2; Ylikallio and Suomalainen, 2012). Figure 2 has been adopted and the modified from Reddy and Beal (2008).


A review on mitochondrial restorative mechanism of antioxidants in Alzheimer's disease and other neurological conditions.

Kumar A, Singh A - Front Pharmacol (2015)

Role of mitochondria in AD. In early-onset AD, it is hypothesized that mitochondria leads to the generation of free radicals (, H2O2), which in turn decrease cytochrome oxidase activity and inhibit cellular ATP generation. Further in late-onset AD, free generation actives BACE mediated cleavage of Aβ. Again Aβ enter into the mitochondria and induces free radicals that leads to disruptions of ETC, decrease in cytochrome oxidase activity and the inhibition of ATP which finally leads to neuronal damage and cognitive decline in AD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585235&req=5

Figure 2: Role of mitochondria in AD. In early-onset AD, it is hypothesized that mitochondria leads to the generation of free radicals (, H2O2), which in turn decrease cytochrome oxidase activity and inhibit cellular ATP generation. Further in late-onset AD, free generation actives BACE mediated cleavage of Aβ. Again Aβ enter into the mitochondria and induces free radicals that leads to disruptions of ETC, decrease in cytochrome oxidase activity and the inhibition of ATP which finally leads to neuronal damage and cognitive decline in AD.
Mentions: It is well documented that reduced cytochrome oxidase activity is correlated with an increased defects in mtDNA in AD (Swerdlow et al., 2014). The brain, due to the presence of high lipid content, high oxygen consumption and low antioxidant defenses, remains the most vulnerable organ to oxidative stress. It is also well documented that free radical generation by mitochondrial dysfunction affect both in neurons and astrocytes during AD. There is also generation of free radicals () produced in mitochondrial ETC complexes I and III and enzymes of the TCA (α-ketoglutarate dehydrogenase) in AD. From inner mitochondrial membranes hydrogen peroxide (H2O2) and is released to the outer side (cytoplasm) which finally causes oxidation of cytoplasmic proteins (Figure 2; Ylikallio and Suomalainen, 2012). Figure 2 has been adopted and the modified from Reddy and Beal (2008).

Bottom Line: Increasing evidence has indicated that mitochondrial dysfunction displays significant role in the pathophysiological processes of AD.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.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University , Chandigarh, India.

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.

No MeSH data available.


Related in: MedlinePlus