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Metabolomic Profiling in Children with Celiac Disease: Beyond the Gluten-Free Diet.
Martín-Masot, R, Jiménez-Muñoz, M, Herrador-López, M, Navas-López, VM, Obis, E, Jové, M, Pamplona, R, Nestares, T
Nutrients. 2023;(13)
Abstract
Celiac disease (CD) is included in the group of complex or multifactorial diseases, i.e., those caused by the interaction of genetic and environmental factors. Despite a growing understanding of the pathophysiological mechanisms of the disease, diagnosis is still often delayed and there are no effective biomarkers for early diagnosis. The only current treatment, a gluten-free diet (GFD), can alleviate symptoms and restore intestinal villi, but its cellular effects remain poorly understood. To gain a comprehensive understanding of CD's progression, it is crucial to advance knowledge across various scientific disciplines and explore what transpires after disease onset. Metabolomics studies hold particular significance in unravelling the complexities of multifactorial and multisystemic disorders, where environmental factors play a significant role in disease manifestation and progression. By analyzing metabolites, we can gain insights into the reasons behind CD's occurrence, as well as better comprehend the impact of treatment initiation on patients. In this review, we present a collection of articles that showcase the latest breakthroughs in the field of metabolomics in pediatric CD, with the aim of trying to identify CD biomarkers for both early diagnosis and treatment monitoring. These advancements shed light on the potential of metabolomic analysis in enhancing our understanding of the disease and improving diagnostic and therapeutic strategies. More studies need to be designed to cover metabolic profiles in subjects at risk of developing the disease, as well as those analyzing biomarkers for follow-up treatment with a GFD.
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Lipid Adaptations against Oxidative Challenge in the Healthy Adult Human Brain.
Jové, M, Mota-Martorell, N, Obis, È, Sol, J, Martín-Garí, M, Ferrer, I, Portero-Otín, M, Pamplona, R
Antioxidants (Basel, Switzerland). 2023;(1)
Abstract
It is assumed that the human brain is especially susceptible to oxidative stress, based on specific traits such as a higher rate of mitochondrial free radical production, a high content in peroxidizable fatty acids, and a low antioxidant defense. However, it is also evident that human neurons, although they are post-mitotic cells, survive throughout an entire lifetime. Therefore, to reduce or avoid the impact of oxidative stress on neuron functionality and survival, they must have evolved several adaptive mechanisms to cope with the deleterious effects of oxidative stress. Several of these antioxidant features are derived from lipid adaptations. At least six lipid adaptations against oxidative challenge in the healthy human brain can be discerned. In this work, we explore the idea that neurons and, by extension, the human brain is endowed with an important arsenal of non-pro-oxidant and antioxidant measures to preserve neuronal function, refuting part of the initial premise.
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Hakuna MAM-Tata: Investigating the role of mitochondrial-associated membranes in ALS.
Bernal, AF, Mota, N, Pamplona, R, Area-Gomez, E, Portero-Otin, M
Biochimica et biophysica acta. Molecular basis of disease. 2023;(6):166716
Abstract
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease leading to selective and progressive motor neuron (MN) death. Despite significant heterogeneity in pathogenic and clinical terms, MN demise ultimately unifies patients. Across the many disturbances in neuronal biology present in the disease and its models, two common trends are loss of calcium homeostasis and dysregulations in lipid metabolism. Since both mitochondria and endoplasmic reticulum (ER) are essential in these functions, their intertwin through the so-called mitochondrial-associated membranes (MAMs) should be relevant in this disease. In this review, we present a short overview of MAMs functional aspects and how its dysfunction could explain a substantial part of the cellular disarrangements in ALS's natural history. MAMs are hubs for lipid synthesis, integrating glycerophospholipids, sphingolipids, and cholesteryl ester metabolism. These lipids are essential for membrane biology, so there should be a close coupling to cellular energy demands, a role that MAMs may partially fulfill. Not surprisingly, MAMs are also host part of calcium signaling to mitochondria, so their impairment could lead to mitochondrial dysfunction, affecting oxidative phosphorylation and enhancing the vulnerability of MNs. We present data supporting that MAMs' maladaptation could be essential to MNs' vulnerability in ALS.
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New insights into human prefrontal cortex aging with a lipidomics approach.
Jové, M, Mota-Martorell, N, Torres, P, Portero-Otin, M, Ferrer, I, Pamplona, R
Expert review of proteomics. 2021;(5):333-344
Abstract
INTRODUCTION Human prefrontal cortex (hPFC) is a recent evolutionarily developed brain region involved in cognitive functions. Human cognitive functions decline during aging. Yet the molecular mechanisms underlying the functional deterioration of the neural cells of this brain region still remain to be fully described. AREAS COVERED In this review, we explore the role of lipids in hPFC aging. Firstly, we briefly consider the approaches used to identify lipid species in brain tissue with special attention paid to a lipidomics analysis. Then, as the evolution process has conferred a specific lipid profile on the hPFC, we consider the lipidome of hPFC. In addition, the role of lipids in hPFC aging, and in particular, the cognitive decline associated with aging, is discussed. Finally, nutritional and pharmacological interventions designed to modulate this process are examined. It is suggested that the dysfunction of key cellular processes secondarily to the damage of lipid membrane underlies the cognitive decline of hPFC during aging. EXPERT OPINION Lipidomics methods are and will continue to be key tools in the effort to gain additional insights into the aging of the human brain.
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Redox lipidomics to better understand brain aging and function.
Pamplona, R, Borras, C, Jové, M, Pradas, I, Ferrer, I, Viña, J
Free radical biology & medicine. 2019;:310-321
Abstract
Human prefrontal cortex (PFC) is a recently evolutionary emerged brain region involved in cognitive functions. Human cognitive abilities decline during aging. Yet the molecular mechanisms that sustain the preservation or deterioration of neurons and PFC functions are unknown. In this review, we focus on the role of lipids in human PFC aging. As the evolution of brain lipid concentrations is particularly accelerated in the human PFC, conferring a specific lipid profile, a brief approach to the lipidome of PFC was consider along with the relationship between lipids and lipoxidative damage, and the role of lipids in human PFC aging. In addition, the specific targets of lipoxidative damage in human PFC, the affected biological processes, and their potential role in the cognitive decline associated with aging are discussed. Finally, interventions designed to modify this process are considered. We propose that the dysfunction of key biological processes due to selective protein lipoxidation damage may have a role the cognitive decline of PFC during aging.