Mitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential

Mi, Yashi; Qi, Guoyuan; Brinton, Roberta Dı́az; Yin, Fei

doi:10.1089/ars.2020.8070

Cited by 21 publications

(24 citation statements)

References 195 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some dietary interventions, i.e., ketogenic diet, can increase the level of ketone bodies in the blood. It was shown that utilization of ketone bodies as an energy source by neurons may improve brain health (reviewed in [ 85 ]). In particular, in neurons ketone bodies were shown to promote mitochondrial biogenesis mediated by the brain-derived neurotrophic factor (BDNF).…”

Section: Midlife Increase In Mitochondrial Function Followed By Its Subsequent Declinementioning

confidence: 99%

“…Similarly, an increase in mitochondrial activity and decrease in the levels of lipid peroxidation products was observed in brains of female mice fed with whey protein [ 121 ]. A protective effect of vitamin C in mouse models of Alzheimer’s disease (reviewed by [ 85 ]) was also reported. Mitochondrially-targeted antioxidants such as MitoQ and SkQ, ubiquinone and plastoquinone derivatives conjugated with penetrating cation triphenylphosphonium, seem to be even more promising [ 85 , 122 ].…”

Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

“…A protective effect of vitamin C in mouse models of Alzheimer’s disease (reviewed by [ 85 ]) was also reported. Mitochondrially-targeted antioxidants such as MitoQ and SkQ, ubiquinone and plastoquinone derivatives conjugated with penetrating cation triphenylphosphonium, seem to be even more promising [ 85 , 122 ]. Because of the role of ROS in cell signaling their overall decrease may be ineffective or even detrimental.…”

Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

See 2 more Smart Citations

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

et al. 2021

View full text Add to dashboard Cite

Neural tissue is one of the main oxygen consumers in the mammalian body, and a plentitude of metabolic as well as signaling processes within the brain is accompanied by the generation of reactive oxygen (ROS) and nitrogen (RNS) species. Besides the important signaling roles, both ROS and RNS can damage/modify the self-derived cellular components thus promoting neuroinflammation and oxidative stress. While previously, the latter processes were thought to progress linearly with age, newer data point to midlife as a critical turning point. Here, we describe (i) the main pathways leading to ROS/RNS generation within the brain, (ii) the main defense systems for their neutralization and (iii) summarize the recent literature about considerable changes in the energy/ROS homeostasis as well as activation state of the brain’s immune system at midlife. Finally, we discuss the role of calorie restriction as a readily available and cost-efficient antiaging and antioxidant lifestyle intervention.

show abstract

Section: Midlife Increase In Mitochondrial Function Followed By Its Subsequent Declinementioning

confidence: 99%

Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

Section: Contribution Of Mitochondrially Produced Ros To Age-related Changes In Signaling Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Mitochondria are involved in neuronal plasticity and provide ATP for processes involved in neurite outgrowth ( Todorova and Blokland, 2017 ). Impairment in the mitochondria of neurons is one of the earliest events before clinical diagnosis during the pathological progression of AD ( Mi et al, 2020 ). We found that mitochondrial dysfunction-induced apoptosis was related to the direct effect of Aβ 25–35 .…”

Section: Discussionmentioning

confidence: 99%

SIRT1 Is Involved in the Neuroprotection of Pterostilbene Against Amyloid β 25–35-Induced Cognitive Deficits in Mice

Zhu

Zhang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposits and neurofibrillary tangles. Pterostilbene (PTE), a bioactive component mainly in blueberries, is found to have neuroprotective properties. However, the specific underlying mechanisms of PTE in protecting AD remain unclear. Herein, we explored its effects on Aβ25–35-induced neuronal damage in vivo and in vitro and further compared the roles with its structural analog resveratrol (RES) in improving learning–memory deficits. We found that intragastric administration of PTE (40 mg/kg) displayed more effective neuroprotection on Aβ25–35-induced cognitive dysfunction assessed using the novel object test, Y-maze test, and Morris water maze test. Then, we found that PTE improved neuronal plasticity and alleviated neuronal loss both in vivo and in vitro. Additionally, PTE upregulated the expression of sirtuin-1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD), and inhibited mitochondria-dependent apoptosis in the Aβ25–35-treated group. However, SIRT1 inhibitor EX527 reversed the neuroprotection and induced a drop in mitochondrial membrane potential in PTE-treated primary cortical neurons. Our data suggest that PTE’s enhancing learning–memory ability and improving neuroplasticity might be related to inhibiting mitochondria-dependent apoptosis via the antioxidant effect regulated by SIRT1/Nrf2 in AD.

show abstract

“…The deposition of plaques and NFTs initiate a neuroinflammatory response through the activation of microglia and astrocytes that react to disturbances such as aggregated proteins and promote the release of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumour necrosis factor alpha (TNF-α), in addition to reactive oxygen species (ROS) [ 22 ]. Changes to mitochondrial function and disruption to brain bioenergetics have been well documented as early events in AD progression [ 23 ]. Evidence suggests that accumulating Aβ binds to mitochondrial proteins, resulting in dysfunction and an increase in ROS formation [ 24 ].…”

Section: Alzheimer´s Disease Pathology Hallmarksmentioning

confidence: 99%

Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer’s Disease

2022

View full text Add to dashboard Cite

Characterising Alzheimer’s disease (AD) as a metabolic disorder of the brain is gaining acceptance based on the pathophysiological commonalities between AD and major metabolic disorders. Therefore, metabolic interventions have been explored as a strategy for brain energetic rescue. Amongst these, medium-chain fatty acid (MCFA) supplementations have been reported to rescue the energetic failure in brain cells as well as the cognitive decline in patients. Short-chain fatty acids (SCFA) have also been implicated in AD pathology. Due to the increasing therapeutic interest in metabolic interventions and brain energetic rescue in neurodegenerative disorders, in this review, we first summarise the role of SCFAs and MCFAs in AD. We provide a comparison of the main findings regarding these lipid species in established AD animal models and recently developed human cell-based models of this devastating disorder.

show abstract

Mitochondria-Targeted Therapeutics for Alzheimer's Disease: The Good, the Bad, the Potential

Cited by 21 publications

References 195 publications

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

Oxidative Stress and Energy Metabolism in the Brain: Midlife as a Turning Point

SIRT1 Is Involved in the Neuroprotection of Pterostilbene Against Amyloid β 25–35-Induced Cognitive Deficits in Mice

Fats, Friends or Foes: Investigating the Role of Short- and Medium-Chain Fatty Acids in Alzheimer’s Disease

Contact Info

Product

Resources

About