Potential roles of PINK1 for increased PGC-1α-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer disease and diabetes

Choi, Joungil; Ravipati, Avinash; Nimmagadda, Vamshi K.C.; Schubert, Manfred; Castellani, Rudolph J.; Russell, James W.

doi:10.1016/j.mito.2014.09.005

Cited by 58 publications

(49 citation statements)

References 38 publications

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“…Disruption of this process leads to bioenergetic failure and intracellular lipid accumulation. This ectopic fatty acid accumulation further inhibits mitochondrial function, leading to increased oxidative stress and apoptotic neuronal cell death in diabetes [39, 40]. Additionally, elevated levels of ketone bodies (acetoacetate, 3-hydroxybutyrate and acetone) in our study suggest that present of transformation of energy metabolism substrate.…”

Section: Discussionmentioning

confidence: 66%

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Zhou

Lian

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mitochondrial perturbation is a well-established cause of cognitive decline, but as yet it is unclear how mitochondria-associated neuronal abnormalities in type 1 diabetic (T1DM) brain contribute to cognitive decline. Methods: The streptozotocin (STZ)-induced mouse model of T1DM was used. The Morris water maze test was applied to assess the effect of T1DM on learning and memory. We detected changes in mitochondrial morphology, function and dynamics. Furthermore, we employed metabolomic analysis to reveal the underlying mechanisms of mitochondrial perturbation which contribute to cognitive decline. Results: Our results show that T1DM impairs mitochondrial dynamics, morphology and function in neurons, associated with a decline in cognitive ability. Metabolomic analyses revealed that T1DM mainly affects metabolic pathways involved in mitochondrial energy failure and impairs the antioxidative system. Conclusion: These results lay the basis for understanding the underlying mitochondria-associated causes of T1DM-associated cognitive decline and may provide a potential treatment strategy for this condition in future.

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Section: Discussionmentioning

confidence: 66%

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Zhou

Lian

Zhang

et al. 2018

Cell Physiol Biochem

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“…Moreover, some reports found alterations in FAO in neurodegenerative disorders and also neuroprotective effects associated to the activation of FAO, which suggest that Nrf2-induced FAO can be a potential therapeutic target. For example, it was shown that the levels of two of the main enzymes for β-oxidation, acyl-coenzyme A dehydrogenase and mitochondrial trifunctional enzyme subunit α are reduced in AD patients (Choi et al, 2014). In a different study, 3-hydroxyacylCoA dehydrogenase, which catalyzes the oxidation of 3-hydroxyacyl-CoAs in the mitochondrial FAO, was shown to protect against the MPTP-induced impairment of oxidative phosphorylation and ATP production in this model of PD (Tieu et al, 2004).…”

Section: Nrf2 and Lipid Metabolismmentioning

confidence: 87%

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Esteras¹,

Dinkova‐Kostova²,

Abramov³

2016

Biological Chemistry

143

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Abstract:The nuclear factor erythroid-derived 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor wellknown for its function in controlling the basal and inducible expression of a variety of antioxidant and detoxifying enzymes. As part of its cytoprotective activity, increasing evidence supports its role in metabolism and mitochondrial bioenergetics and function. Neurodegenerative diseases are excellent candidates for Nrf2-targeted treatments. Most neurodegenerative conditions such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia and Friedreich's ataxia are characterized by oxidative stress, misfolded protein aggregates, and chronic inflammation, the common targets of Nrf2 therapeutic strategies. Together with them, mitochondrial dysfunction is implicated in the pathogenesis of most neurodegenerative disorders. The recently recognized ability of Nrf2 to regulate intermediary metabolism and mitochondrial function makes Nrf2 activation an attractive and comprehensive strategy for the treatment of neurodegenerative disorders. This review aims to focus on the potential therapeutic role of Nrf2 activation in neurodegeneration, with special emphasis on mitochondrial bioenergetics and function, metabolism and the role of transporters, all of which collectively contribute to the cytoprotective activity of this transcription factor.

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“…Prevention of mitochondrial dysfunction is thought to be the main therapeutic strategy for the delay in progression of neurodegenerative disorders, including Alzheimer's, Parkinson's, and prion disease . Recent studies have shown that the melatonin‐mediated autophagy activation prevents prion‐mediated neurotoxicity via protection of mitochondrial function .…”

Section: Discussionmentioning

confidence: 99%

Melatonin regulates the autophagic flux via activation of alpha‐7 nicotinic acetylcholine receptors

Jeong

Park

2015

Journal of Pineal Research

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Our previous study suggested that melatonin-mediated neuroprotective effects are related with the activation of autophagy. However, the mechanism of melatonin-mediated autophagic activation in prion-mediated mitochondrial damage is not reported. Alpha-7 nicotinic acetylcholine receptors (α7nAchR) is a member of nicotinic acetylcholine receptors, and α7nAchR activation regulates via melatonin. Thus, we hypothesized that melatonin-mediated neuroprotective effect related with to autophagy pathway as a result of α7nAchR regulation. Inactivation of α7nAchR inhibited melatonin-mediated autophagic activation and protective effect against prion-mediated mitochondrial neurotoxicity. Also, knockdown of ATG5 blocked the melatonin-mediated neuroprotection and did not influence to the activation of α7nAchR caused by melatonin. This report is the first study demonstrating that melatonin-mediated autophagic activation regulates via modulation of α7nAchR signals, and upregulation of α7nAchR signals induced by melatonin plays a pivotal role in neuroprotection of prion-mediated mitochondrial neurotoxicity. Our results suggested that regulator of α7 nAChR signals including melatonin may have used for neuroprotective strategies for the neurodegenerative disorders including prion diseases.

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Potential roles of PINK1 for increased PGC-1α-mediated mitochondrial fatty acid oxidation and their associations with Alzheimer disease and diabetes

Cited by 58 publications

References 38 publications

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Nrf2 activation in the treatment of neurodegenerative diseases: a focus on its role in mitochondrial bioenergetics and function

Melatonin regulates the autophagic flux via activation of alpha‐7 nicotinic acetylcholine receptors

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