CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson’s disease

Morales-García, José A.; Giné, Elena; Hernández-Encinas, Elena; Aguilar-Morante, Diana; Sierra-Magro, Ana; Sanz-SanCristóbal, Marina; Alonso‐Gil, Sandra; Sánchez-Lanzas, Raúl; Castaño, José G.; Pérez-Castillo, Ana

doi:10.1038/s41598-017-13269-4

Cited by 10 publications

(12 citation statements)

References 49 publications

(52 reference statements)

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“…Jak-Stat signaling, including Stat3, is up-regulated in prion, Alzheimer's, and Huntington's diseases [43,59], and promotes astrogliosis in scrapie-infected mice [60]. Cebpb regulates expression of delta secretase to modify amyloid plaque formation in AD [61] and promotes glial activation in Parkinson's disease models [62]. Srebf1 links lipogenesis to mitophagy and sporadic Parkinson's disease [63], and knockdown of Srebf1 blocks the translocation of Parkin into mitochondria, thereby decreasing mitophagy [64].…”

Section: Discussionmentioning

confidence: 99%

Core transcriptional regulatory circuits in prion diseases

et al. 2020

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Complex diseases involve dynamic perturbations of pathophysiological processes during disease progression. Transcriptional programs underlying such perturbations are unknown in many diseases. Here, we present core transcriptional regulatory circuits underlying early and late perturbations in prion disease. We first identified cellular processes perturbed early and late using time-course gene expression data from three prion-infected mouse strains. We then built a transcriptional regulatory network (TRN) describing regulation of early and late processes. We found over-represented feed-forward loops (FFLs) comprising transcription factor (TF) pairs and target genes in the TRN. Using gene expression data of brain cell types, we further selected active FFLs where TF pairs and target genes were expressed in the same cell type and showed correlated temporal expression changes in the brain. We finally determined core transcriptional regulatory circuits by combining these active FFLs. These circuits provide insights into transcriptional programs for early and late pathophysiological processes in prion disease.

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Section: Discussionmentioning

confidence: 99%

Core transcriptional regulatory circuits in prion diseases

et al. 2020

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“…CCAAT/enhancer binding protein ß (C/EBPß) is a transcription factor whose role in pathogenesis of PD has been reported. It regulates the expression of genes involved in inflammatory processes and brain injury ( Morales-Garcia et al, 2017 ). Studies suggest important role of cyclooxygenase-2 (COX-2) enzyme in secondary activation of microglia, in the progression of the inflammatory response, and in the progressive loss of dopaminergic neurons ( Vijitruth et al, 2006 ).…”

Section: Pathophysiology Of Parkinson’s Diseasementioning

confidence: 99%

Anti-Parkinson Potential of Silymarin: Mechanistic Insight and Therapeutic Standing

Ullah

Khan

2018

Front. Pharmacol.

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Parkinson’s disease (PD) involves aggregation of α-synuclein and progressive loss of dopaminergic neurons. Pathogenesis of PD may also be related to one’s genetic background. PD is most common among geriatric population and approximately 1–2% of population suffers over age 65 years. Currently no successful therapies are in practice for the management of PD and available therapies tend to decrease the symptoms of PD only. Furthermore, these are associated with diverse range of adverse effects profile. The neuroprotective effects of polyphenols are widely studied and documented. Among phytochemicals, silymarin is one of the most widely used flavonoids because of its extensive therapeutic properties and has been indicated in pathological conditions of prostate, CNS, lungs, skin, liver, and pancreas. Silymarin is a mixture of flavonolignans (silybin, isosilybin, and silychristin), small amount of flavonoids (taxifolin), fatty acids, and other polyphenolic compounds extracted from the dried fruit of Silybum marianum and is clinically used for hepatoprotective effects since ancient times. Neuroprotective effects of silymarin have been studied in various models of neurological disorders such as Alzheimer’s disease, PD, and cerebral ischemia. The aim of the present study is to provide a comprehensive review of the recent literature exploring the effects of silymarin administration on the progression of PD. Reducing oxidative stress, inflammatory cytokines, altering cellular apoptosis machinery, and estrogen receptor machinery are mechanisms that are responsible for neuroprotection by silymarin, as discussed in this review. Additionally, because of poor aqueous solubility, the bioavailability of silymarin is low and only 23–47% of silymarin reaches systemic circulation after oral administration. Our primary focus is on the chemical basis of the pharmacology of silymarin in the treatment of PD and its mechanisms and possible therapeutic/clinical status while addressing the bioavailability limitation.

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“…Notably, in the presence of αSyn–antibody complexes, CA suppresses the release of IL-1β from hiMG, indirectly indicating NLRP3 inflammasome inhibition [ 243 ]. The upregulation of CEBPβ expression, a member of the CCAAT-enhancer-binding protein (CEBP) family, is associated with the increased expression of NFkB target genes, resulting in glia-mediated neuronal damage [ 244 , 245 , 246 ].…”

Section: Neuroprotective Potential Of β-Caryophyllene and Carnosic Ac...mentioning

confidence: 99%

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

2022

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Inflammation and oxidative stress are interlinked and interdependent processes involved in many chronic diseases, including neurodegeneration, diabetes, cardiovascular diseases, and cancer. Therefore, targeting inflammatory pathways may represent a potential therapeutic strategy. Emerging evidence indicates that many phytochemicals extracted from edible plants have the potential to ameliorate the disease phenotypes. In this scenario, ß-caryophyllene (BCP), a bicyclic sesquiterpene, and carnosic acid (CA), an ortho-diphenolic diterpene, were demonstrated to exhibit anti-inflammatory, and antioxidant activities, as well as neuroprotective and mitoprotective effects in different in vitro and in vivo models. BCP essentially promotes its effects by acting as a selective agonist and allosteric modulator of cannabinoid type-2 receptor (CB2R). CA is a pro-electrophilic compound that, in response to oxidation, is converted to its electrophilic form. This can interact and activate the Keap1/Nrf2/ARE transcription pathway, triggering the synthesis of endogenous antioxidant “phase 2” enzymes. However, given the nature of its chemical structure, CA also exhibits direct antioxidant effects. BCP and CA can readily cross the BBB and accumulate in brain regions, giving rise to neuroprotective effects by preventing mitochondrial dysfunction and inhibiting activated microglia, substantially through the activation of pro-survival signalling pathways, including regulation of apoptosis and autophagy, and molecular mechanisms related to mitochondrial quality control. Findings from different in vitro/in vivo experimental models of Parkinson’s disease and Alzheimer’s disease reported the beneficial effects of both compounds, suggesting that their use in treatments may be a promising strategy in the management of neurodegenerative diseases aimed at maintaining mitochondrial homeostasis and ameliorating glia-mediated neuroinflammation.

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CCAAT/Enhancer binding protein β silencing mitigates glial activation and neurodegeneration in a rat model of Parkinson’s disease

Cited by 10 publications

References 49 publications

Core transcriptional regulatory circuits in prion diseases

Core transcriptional regulatory circuits in prion diseases

Anti-Parkinson Potential of Silymarin: Mechanistic Insight and Therapeutic Standing

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

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