A novel mechanism of neuroprotection: Blood glutamate grabber

Castillo, José; Loza, Marı́a Isabel; Mirelman, David; Brea, José; Blanco, Miguel; Sobrino, Tomás; Campos, Francisco

doi:10.1177/0271678x15606721

Cited by 79 publications

(80 citation statements)

References 66 publications

(104 reference statements)

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“…), suggesting that further studies on this key multifaceted metabolite and neurotransmitter are recommended to minimize its detrimental effects and boost the neuroprotective ones (Castillo et al . ; Chamorro et al . ; Kim et al .…”

Section: Discussionmentioning

confidence: 99%

Glutamate metabolism in cerebral mitochondria after ischemia and post‐ischemic recovery during aging: relationships with brain energy metabolism

Ferrari

Gorini

Hoyer

et al. 2018

Journal of Neurochemistry

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Glutamate is involved in cerebral ischemic injury, but its role has not been completely clarified and studies are required to understand how to minimize its detrimental effects, contemporarily boosting the positive ones. In fact, glutamate is not only a neurotransmitter, but primarily a key metabolite for brain bioenergetics. Thus, we investigated the relationships between glutamate and brain energy metabolism in an in vivo model of complete cerebral ischemia of 15 min and during post-ischemic recovery after 1, 24, 48, 72, and 96 h in 1-year-old adult and 2-year-old aged rats. The maximum rates (V ) of glutamate dehydrogenase (GlDH), glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were assayed in somatic mitochondria (FM) and in intra-synaptic 'Light' mitochondria and intra-synaptic 'Heavy' mitochondria ones purified from cerebral cortex, distinguishing post- and pre-synaptic compartments. During ischemia, none of the enzymes were modified in adult animals. In aged ones, glutamate-oxaloacetate transaminase was increased in FM and GlDH in intra-synaptic 'Heavy' mitochondria, stimulating glutamate catabolism. During post-ischemic recovery, FM did not show modifications at both ages while, in intra-synaptic mitochondria of adult animals, glutamate catabolism was increased after 1 h of recirculation and decreased after 48 and 72 h, whereas it remained decreased up to 96 h in aged rats. These results, with those previously published about Krebs' cycle and Electron Transport Chain (Villa et al., [2013] Neurochem. Int. 63, 765-781), demonstrate that: (i) V of energy-linked enzymes are different in the various cerebral mitochondria, which (ii) respond differently to ischemia and post-ischemic recovery, also (iii) with respect to aging.

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Section: Discussionmentioning

confidence: 99%

Glutamate metabolism in cerebral mitochondria after ischemia and post‐ischemic recovery during aging: relationships with brain energy metabolism

Ferrari

Gorini

Hoyer

et al. 2018

Journal of Neurochemistry

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“…Since accumulation of glutamate can cause neuro-excitotoxic effects, its accumulation was repressed via scavenging of it by pyruvate and oxaloacetate (Castillo et al, 2016;Danbolt et al, 2001;Zlotnik et al, 2012). The weight of the evidence suggests that particularly carbohydrate and energy metabolism are the main components of PD, AD, and ALS development.…”

Section: Figmentioning

confidence: 99%

Metabolic Biomarkers and Neurodegeneration: A Pathway Enrichment Analysis of Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Kori

Aydın

Unal

et al. 2016

OMICS: A Journal of Integrative Biology

122

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Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) lack robust diagnostics and prognostic biomarkers. Metabolomics is a postgenomics field that offers fresh insights for biomarkers of common complex as well as rare diseases. Using data on metabolite-disease associations published in the previous decade (2006-2016) in PubMed, ScienceDirect, Scopus, and Web of Science, we identified 101 metabolites as putative biomarkers for these three neurodegenerative diseases. Notably, uric acid, choline, creatine, L-glutamine, alanine, creatinine, and N-acetyl-L-aspartate were the shared metabolite signatures among the three diseases. The disease-metabolite-pathway associations pointed out the importance of membrane transport (through ATP binding cassette transporters), particularly of arginine and proline amino acids in all three neurodegenerative diseases. When disease-specific and common metabolic pathways were queried by using the pathway enrichment analyses, we found that alanine, aspartate, glutamate, and purine metabolism might act as alternative pathways to overcome inadequate glucose supply and energy crisis in neurodegeneration. These observations underscore the importance of metabolite-based biomarker research in deciphering the elusive pathophysiology of neurodegenerative diseases. Future research investments in metabolomics of complex diseases might provide new insights on AD, PD, and ALS that continue to place a significant burden on global health.

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“…Overactivation of NMDA and AMPA receptors results in neuronal death and dysfunction [43,44]. Induced middle cerebral artery occlusion has been used in numerous cerebral ischemia models [45][46][47][48].…”

Section: Cerebral Ischemiamentioning

confidence: 99%

“…Induced middle cerebral artery occlusion has been used in numerous cerebral ischemia models [45][46][47][48]. In such models, the caudate putamen and cerebral cortex become the ischemic core and penumbra area, respectively [43,44].…”

Section: Cerebral Ischemiamentioning

confidence: 99%