Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

Isopi, Elisa; Granzotto, Alberto; Corona, Carlo; Bomba, Manuela; Ciavardelli, Domenico; Curcio, M. Joan; Canzoniero, Lorella M.T.; Navarra, Riccardo; Lattanzio, Rossano; Piantelli, Mauro; Sensi, Stefano L.

doi:10.1016/j.nbd.2014.11.013

Cited by 57 publications

(59 citation statements)

References 83 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These levetiracetam effects (as well as another antiepileptic topiramate) were also later confirmed for APPswe/PS1dE9 transgenic mice (Shi et al, ). Although both studies used the only cognitive test (Moris water maze), recent reports show the beneficial effect of pyruvate on cognition in 3xTg‐AD mice (Isopi et al, ) and the rat sporadic AD model (Wang et al, ).…”

Section: Short Outline Of Main Glucose Functionsmentioning

confidence: 99%

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

Zilberter

2017

J of Neuroscience Research

169

139

View full text Add to dashboard Cite

Hypometabolism, characterized by decreased brain glucose consumption, is a common feature of many neurodegenerative diseases. Initial hypometabolic brain state, created by characteristic risk factors, may predispose the brain to acquired epilepsy and sporadic Alzheimer's and Parkinson's diseases, which are the focus of this review. Analysis of available data suggests that deficient glucose metabolism is likely a primary initiating factor for these diseases, and that resulting neuronal dysfunction further promotes the metabolic imbalance, establishing an effective positive feedback loop and a downward spiral of disease progression. Therefore, metabolic correction leading to the normalization of abnormalities in glucose metabolism may be an efficient tool to treat the neurological disorders by counteracting their primary pathological mechanisms. Published and preliminary experimental results on this approach for treating Alzheimer's disease and epilepsy models support the efficacy of metabolic correction, confirming the highly promising nature of the strategy. V C 2017 Wiley Periodicals, Inc.

show abstract

Section: Short Outline Of Main Glucose Functionsmentioning

confidence: 99%

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

Zilberter

2017

J of Neuroscience Research

169

139

View full text Add to dashboard Cite

show abstract

“…Pyruvate treatment reduced infarct size and improved neurological functions in a rat middle cerebral artery occlusion model of ischemia (Yu et al, 2005). It also improved cerebral oxidative metabolism and neurological outcomes in rats following cortical contusion injury (Fukushima et al, 2009; Moro and Sutton, 2010), protected against MPTP induced degeneration of neurons and reduced oxidative stress in a mouse model of Parkinson's disease (Huh et al, 2011; Satpute et al, 2013), and reduced cognitive deficits in a mouse model of Alzheimer's disease (Isopi et al, 2015). …”

Section: Metabolic Treatments In Alsmentioning

confidence: 99%

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

Tefera

Borges

2017

Front. Neurosci.

View full text Add to dashboard Cite

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease primarily characterized by loss of motor neurons in brain and spinal cord. The death of motor neurons leads to denervation of muscle which in turn causes muscle weakness and paralysis, decreased respiratory function and eventually death. Growing evidence indicates disturbances in energy metabolism in patients with ALS and animal models of ALS, which are likely to contribute to disease progression. Particularly, defects in glucose metabolism and mitochondrial dysfunction limit the availability of ATP to CNS tissues and muscle. Several metabolic approaches improving mitochondrial function have been investigated in vitro and in vivo and showed varying effects in ALS. The effects of metabolic approaches in ALS models encompass delays in onset of motor symptoms, protection of motor neurons and extension of survival, which signifies an important role of metabolism in the pathogenesis of the disease. There is now an urgent need to test metabolic approaches in controlled clinical trials. In addition, more detailed studies to better characterize the abnormalities in energy metabolism in patients with ALS and ALS models are necessary to develop metabolically targeted effective therapies that can slow the progression of the disease and prolong life for patients with ALS.

show abstract

“…FA and AKG have been proposed to protect cardiac muscles possibly through activating or inhibiting specific transcription factors, such as NF-E2 related factor 2 (NRF2) and hypoxia inducible factor (HIF-1), respectively. In neurons, PA prevents hydrogen peroxide (H 2 O 2 )-induced cell death [8,9], protects the brain against experimental stroke via an anti-inflammatory mechanism [10], and prevents the age-dependent cognitive deficits seen in a mouse model of Alzheimer’s disease [11]. These protections are possibly due to its α-ketoacid structure, which can directly react with H 2 O 2 [8,9].…”

Section: Introductionmentioning

confidence: 99%

Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells

et al. 2017

View full text Add to dashboard Cite

Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2′,7′-dichlorofluorescein diacetate fluorescence. In contrast, none of the KCIs—used at 1 mM—protected against cell death induced by high concentrations of glutamate—another type of oxidative stress-induced neuronal cell death. Because these protective KCIs did not have any toxic effects (at least up to 10 mM), they have potential use for therapeutic intervention against chronic neurodegenerative diseases.

show abstract

Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

Cited by 57 publications

References 83 publications

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

The vicious circle of hypometabolism in neurodegenerative diseases: Ways and mechanisms of metabolic correction

Metabolic Dysfunctions in Amyotrophic Lateral Sclerosis Pathogenesis and Potential Metabolic Treatments

Krebs Cycle Intermediates Protective against Oxidative Stress by Modulating the Level of Reactive Oxygen Species in Neuronal HT22 Cells

Contact Info

Product

Resources

About