Modulation of mitochondrial and inflammatory homeostasis through RIP140 is neuroprotective in an adrenoleukodystrophy mouse model

Ranea-Robles, Pablo; Galino, Jorge; Espinosa, Lluís; Schlüter, Agatha; Ruíz, Montserrat; Calingasan, Noel Y.; Villarroya, Francesc; Naudí, Alba; Pamplona, Reinald; Ferrer, Isidró; Beal, M. Flint; Portero‐Otín, Manuel; Fourcade, Stéphane; Pujol, Aurora

doi:10.1111/nan.12747

Cited by 8 publications

(7 citation statements)

References 68 publications

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“…It negatively regulates energy homeostasis and positively regulates inflammatory response in macrophages, by indirect interaction between Nuclear Factor Kappa B ( NF- κ B ) and TLR -induced proinflammatory cytokines. Depletion of this gene was observed in the interruption of axonal degeneration (Ranea-Robles et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease

Ribeiro-dos-Santos

Brito

Araújo

2023

Front. Aging Neurosci.

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Alzheimer's Disease (AD) is an irreversible neurodegenerative disease clinically characterized by the presence of β-amyloid plaques and tau deposits in various regions of the brain. However, the underlying factors that contribute to the development of AD remain unclear. Recently, the fusiform gyrus has been identified as a critical brain region associated with mild cognitive impairment, which may increase the risk of AD development. In our study, we performed gene co-expression and differential co-expression network analyses, as well as gene-expression-based prediction, using RNA-seq transcriptome data from post-mortem fusiform gyrus tissue samples collected from both cognitively healthy individuals and those with AD. We accessed differential co-expression networks in large cohorts such as ROSMAP, MSBB, and Mayo, and conducted over-representation analyses of gene pathways and gene ontology. Our results comprise four exclusive gene hubs in co-expression modules of Alzheimer's Disease, including FNDC3A, MED23, NRIP1, and PKN2. Further, we identified three genes with differential co-expressed links, namely FAM153B, CYP2C8, and CKMT1B. The differential co-expressed network showed moderate predictive performance for AD, with an area under the curve ranging from 0.71 to 0.76 (+/− 0.07). The over-representation analysis identified enrichment for Toll-Like Receptors Cascades and signaling pathways, such as G protein events, PIP2 hydrolysis and EPH-Epherin mechanism, in the fusiform gyrus. In conclusion, our findings shed new light on the molecular pathophysiology of AD by identifying new genes and biological pathways involved, emphasizing the crucial role of gene regulatory networks in the fusiform gyrus.

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Section: Discussionmentioning

confidence: 99%

The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease

Ribeiro-dos-Santos

Brito

Araújo

2023

Front. Aging Neurosci.

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“…A study found that RIP140 was upregulated in specific tissues that affected cerebral white matter in patients with CALD and spinal cord in ABCD1 mouse models, which may be due to the redox imbalance and excessive ROS required for RIP140 induction. Genic-silenced RIP140 restored mitochondrial function and redox homeostasis and prevented inflammatory response in X-ALD mouse models (36). Thus, inhibition of RIP140 may be regarded as a potential therapeutic target for X-ALD.…”

Section: Other Potential Targets Regulate Redox and Inflammation In X...mentioning

confidence: 96%

“…The exact cause of the onset and damage caused by oxidative stress and inflammation in X-ALD was unknown. However multiple in vivo/in vitro studies have demonstrated that drugs targeting redox imbalance and inflammation effectively improve symptoms and prevent disease progression (8,(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

Chen

Guo

et al. 2022

Front. Nutr.

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X-linked adrenoleukodystrophy (X-ALD) is an inherited disease caused by a mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein. It is characterized by the accumulation of very-long-chain fatty acids (VLCFAs) in body fluids and tissues, leading to progressive demyelination and adrenal insufficiency. ALD has various phenotypes, among which the most common and severe is childhood cerebral adrenoleukodystrophy (CCALD). The pathophysiological mechanisms of ALD remain unclear, but some in vitro/in vivo research showed that VLCFA could induce oxidative stress and inflammation, leading to damage. In addition, the evidence that oxidative stress and inflammation are increased in patients with X-ALD also proves that it is a potential mechanism of brain and adrenal damage. Therefore, normalizing the redox balance becomes a critical therapeutic target. This study focuses on the possible predictors of the severity and progression of X-ALD, the potential mechanisms of pathogenesis, and the promising targeted drugs involved in oxidative stress and inflammation.

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“…Members of the tumor necrosis factor (TNF) superfamily, such as TNF-like weak inducer of apoptosis (TWEAK) and TNF-α, reduce the expression of PGC-1α and mitochondrial biogenesis by activating nuclear factor-κB (NF-κB) [ 52 ]. Interestingly, research has indicated that the absence of receptor-interacting protein 140 significantly increases mitochondrial biogenesis and intracellular FAO [ 53 ]. The exploration of key targets regulating PGC-1α is becoming increasingly important in the study of mitochondrial biogenesis.…”

Section: Molecular Regulations Of Mqcmentioning

confidence: 99%

Mitochondrial quality control in human health and disease

Liu,

Xu,

Liu

et al. 2024

Military Med Res

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Mitochondria, the most crucial energy-generating organelles in eukaryotic cells, play a pivotal role in regulating energy metabolism. However, their significance extends beyond this, as they are also indispensable in vital life processes such as cell proliferation, differentiation, immune responses, and redox balance. In response to various physiological signals or external stimuli, a sophisticated mitochondrial quality control (MQC) mechanism has evolved, encompassing key processes like mitochondrial biogenesis, mitochondrial dynamics, and mitophagy, which have garnered increasing attention from researchers to unveil their specific molecular mechanisms. In this review, we present a comprehensive summary of the primary mechanisms and functions of key regulators involved in major components of MQC. Furthermore, the critical physiological functions regulated by MQC and its diverse roles in the progression of various systemic diseases have been described in detail. We also discuss agonists or antagonists targeting MQC, aiming to explore potential therapeutic and research prospects by enhancing MQC to stabilize mitochondrial function.

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Modulation of mitochondrial and inflammatory homeostasis through RIP140 is neuroprotective in an adrenoleukodystrophy mouse model

Cited by 8 publications

References 68 publications

The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease

The fusiform gyrus exhibits differential gene-gene co-expression in Alzheimer's disease

The Role of Oxidative Stress and Inflammation in X-Link Adrenoleukodystrophy

Mitochondrial quality control in human health and disease

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