Article
Biochemistry & Molecular Biology
Sara Pagnotta, Antonella Tramutola, Eugenio Barone, Fabio Di Domenico, Valeria Pittala, Loredana Salerno, Valentina Folgiero, Matteo Caforio, Franco Locatelli, Stefania Petrini, D. Allan Butterfield, Marzia Perluigi
Summary: This study focuses on the role of BACH1/NRF2 ratio in the regulation of antioxidant response and its impact on patients with Down syndrome. The results show that overexpression of BACH1 disrupts the induction of antioxidant response genes, leading to oxidative damage accumulation. Additionally, administration of CAPE and VP961 promotes NRF2 nuclear translocation in cells from Down syndrome patients, improving antioxidant response.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Manuj Ahuja, Navneet Ammal Kaidery, Debashis Dutta, Otis C. Attucks, Eliot H. Kazakov, Irina Gazaryan, Mitsuyo Matsumoto, Kazuhiko Igarashi, Sudarshana M. Sharma, Bobby Thomas
Summary: Parkinson's disease is a common neurodegenerative disorder characterized by the loss of dopaminergic neurons. Although the exact cause is unclear, oxidative stress, mitochondrial dysfunction, neuroinflammation, and disruption of calcium homeostasis have been proposed as contributing factors. While drugs targeting these pathways have shown promise in preclinical models, a more effective therapeutic approach involving the activation of the Nrf2/Bach1 signaling pathway is being explored. This review discusses the potential benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 for the treatment of Parkinson's disease.
Article
Multidisciplinary Sciences
Sara Cazzaro, Jung-A A. Woo, Xinming Wang, Tian Liu, Shanon Rego, Teresa R. Kee, Yeojung Koh, Edwin Vazquez-Rosa, Andrew A. Pieper, David E. Kang
Summary: Oxidative damage is an early driver of pathology in Alzheimer's disease and related dementias. The Slingshot homolog-1 (SSH1) acts as a counterweight to neuroprotective Nrf2 and drives oxidative damage by suppressing Nrf2 signaling and enhancing Keap1-Nrf2 interaction. Inhibiting SSH1-mediated Nrf2 suppression may provide new neuroprotective therapies for AD and related dementias.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Denise Mafra, Livia Alvarenga, Milena B. Stockler-Pinto, Lia S. Nakao, Peter Stenvinkel, Paul G. Shiels
Summary: Bach1 forms nuclear heterodimers with sMaf, which antagonize the function of Nrf2. Studies have shown dysregulation of Nrf2 and Bach1 expression in chronic diseases. Therefore, investigating Nrf2 activators and Bach1 inhibitors as potential therapeutics for chronic diseases is necessary.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Biochemistry & Molecular Biology
Chiara Lanzillotta, Antonella Tramutola, Graziella Di Giacomo, Federico Marini, D. Allan Butterfield, Fabio Di Domenico, Marzia Perluigi, Eugenio Barone
Summary: Research has shown that Down syndrome shares many common features with early onset Alzheimer's disease, including defects in brain insulin resistance, oxidative stress, and protein activation status in synaptic plasticity mechanisms. These abnormalities appear early in DS model mice, which may contribute to the development of AD in DS.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Review
Cell Biology
Mathew George, Matthan Tharakan, John Culberson, Arubala P. Reddy, P. Hemachandra Reddy
Summary: Nrf2 is a crucial transcription factor that regulates gene expression in healthy and disease states. It plays a vital role in oxidative stress, mitochondrial function, autophagy, and is closely associated with aging and neurodegenerative diseases.
AGEING RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Rui-xuan Wang, Xing Gu, Si-xue Zhang, Yan-jun Zhao, Hong-jun Zhang, Fei-yan Li
Summary: This study aimed to investigate the role of BACH1 in the pathophysiological process of acute lung injury (ALI) with a focus on ferroptosis. The results showed that BACH1 expression was increased upon exposure to LPS, and its deletion exerted anti-inflammatory effects and reduced oxidative stress damage and ferroptosis induced by LPS. Mechanistically, the beneficial effects of BACH1 inhibition were mediated through the Nrf2/HO-1 signaling pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Neurosciences
Yue Fu, Jianping Jia
Summary: The study demonstrates that ISL can reduce inflammatory cytokines and nitric oxide production in BV2 cells stimulated with AβO, alleviate morphological changes, and suppress inflammation and oxidative stress through Nrf2/NF-κB signaling pathway regulation.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Pharmacology & Pharmacy
Miaomiao Meng, Lijuan Zhang, Di Ai, Hongyun Wu, Wei Peng
Summary: Beta-asarone can reduce oxidative stress and neuronal damage induced by A beta, potentially through modulating the PI3K/Akt/Nrf2 signaling pathway, making it a promising therapy for Alzheimer's disease.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Paolo Tucci, Roberta Lattanzi, Cinzia Severini, Luciano Saso
Summary: In this review, we present the scientific literature supporting the role of nuclear transcription factor-2 (Nrf2) in Huntington's disease (HD) and the potential prophylactic and therapeutic role of this compound.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Chemistry, Medicinal
Claudia Bento-Pereira, Albena T. Dinkova-Kostova
Summary: Parkinson's disease is a progressive neurodegenerative disorder for which no disease-modifying therapies are available. Factors like age, genetic predisposition, and environmental stressors are known to increase the risk of developing PD. Activation of Nrf2 has shown to be beneficial in cellular and animal models of PD.
MEDICINAL RESEARCH REVIEWS
(2021)
Review
Pharmacology & Pharmacy
Xin-xing Yang, Rong Yang, Feng Zhang
Summary: Parkinson's disease is a common and chronic degenerative disease in the central nervous system. The main pathology involves the loss of dopaminergic neurons and the formation of Lewy bodies. The pathogenesis of PD is influenced by various independent factors, and regulating the Nrf2 pathway may be a promising strategy for preventing and treating PD.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Clinical Neurology
Alessia Filippone, Domenico Pratico
Summary: Intracellular protein trafficking through the endosomes is crucial for normal neuronal function. Dysfunctions in the endosome system, particularly through the recycling, degradation, and retrograde pathways, are common in neurodegenerative diseases like Alzheimer's and Down syndrome. Two major routes, mediated by the retromer complex and the newly discovered retriever system, play key roles in endosomal transport and could be potential therapeutic targets in these diseases.
ANNALS OF NEUROLOGY
(2021)
Review
Biochemistry & Molecular Biology
Darius J. R. Lane, Billie Metselaar, Mark Greenough, Ashley I. Bush, Scott J. Ayton
Summary: Ferroptosis is a cell death mechanism dependent on iron and lipid peroxidation, with potential implications in various neurodegenerative diseases. The main cellular protector against ferroptosis is glutathione peroxidase 4 (GPX4). The NRF2 signaling pathway plays a key role in regulating ferroptosis.
MOLECULAR MECHANISMS OF NEURODEGENERATION
(2021)
Article
Medicine, General & Internal
Laia Montoliu-Gaya, Daniel Alcolea, Nicholas J. Ashton, Jordi Pegueroles, Johannes Levin, Beatriz Bosch, Juan Lantero-Rodriguez, Maria Carmona-Iragui, Olivia Wagemann, Mircea Balasa, Przemyslaw Radoslaw Kac, Isabel Barroeta, Albert Llado, Wagner S. Brum, Laura Videla, Fernando Gonzalez-Ortiz, Bessy Benejam, Javier Jose Arranz Martinez, Thomas K. Karikari, Georg Nuebling, Alexandre Bejanin, Andrea L. Benedet, Rafael Blesa, Alberto Lleo, Kaj Blennow, Raquel Sanchez-Valle, Henrik Zetterberg, Juan Fortea
Summary: This study found that plasma GFAP levels are associated with the diagnosis and progression of Alzheimer's disease in adults with Down syndrome, indicating its potential as a biomarker. This biomarker may have applications in clinical practice and clinical trials.
Article
Clinical Neurology
Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone
Summary: The study found that nEVs isolated from DS children showed a significant increase in insulin resistance marker pIRS1(Ser636) and hyperactivation of the Akt/mTOR/p70S6K pathway downstream from IRS1, possibly driven by higher inhibition of PTEN. Additionally, high levels of pGSK3 beta(Ser9) were also observed. These alterations in the insulin-signaling/mTOR pathways are believed to be early events in the DS brain, contributing to the cognitive dysfunction and intellectual disability seen in this unique population.
ALZHEIMERS & DEMENTIA
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
D. Allan Butterfield, Eugenio Barone, Fabio Di Domenico, Marzia Perluigi
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Editorial Material
Cell Biology
Eugenio Barone
NEURAL REGENERATION RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Sara Pagnotta, Antonella Tramutola, Eugenio Barone, Fabio Di Domenico, Valeria Pittala, Loredana Salerno, Valentina Folgiero, Matteo Caforio, Franco Locatelli, Stefania Petrini, D. Allan Butterfield, Marzia Perluigi
Summary: This study focuses on the role of BACH1/NRF2 ratio in the regulation of antioxidant response and its impact on patients with Down syndrome. The results show that overexpression of BACH1 disrupts the induction of antioxidant response genes, leading to oxidative damage accumulation. Additionally, administration of CAPE and VP961 promotes NRF2 nuclear translocation in cells from Down syndrome patients, improving antioxidant response.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Flavia Agata Cimini, Marzia Perluigi, Ilaria Barchetta, Maria Gisella Cavallo, Eugenio Barone
Summary: The review highlights the significance of the insulin signaling pathway and the regulatory role of biliverdin reductase-A in insulin signaling, as well as its impact on cell dysfunctions in metabolic and neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
News Item
Clinical Neurology
Marzia Perluigi, Eugenio Barone
Summary: The use of proteomics approach reveals that changes in protein expression associated with Alzheimer's disease may not always be reflected in changes in RNA levels, emphasizing the importance of directly studying proteomic changes to fully understand the pathogenesis of Alzheimer's disease.
NATURE REVIEWS NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chirag Vasavda, Evan R. Semenza, Jason Liew, Ruchita Kothari, Ryan S. Dhindsa, Shruthi Shanmukha, Anthony Lin, Robert Tokhunts, Cristina Ricco, Adele M. Snowman, Lauren Albacarys, Francesco Pastore, Cristian Ripoli, Claudio Grassi, Eugenio Barone, Michael D. Kornberg, Xinzhong Dong, Bindu D. Paul, Solomon H. Snyder
Summary: Synapses play a crucial role in connecting neurons and transmitting information. This study investigates the role of the enzyme biliverdin reductase (BVR) in synaptic function and plasticity. The findings suggest that BVR acts as a bridge between key signaling molecules in synaptic adhesion pathways, and its absence leads to deficits in learning and memory.
Article
Biochemistry & Molecular Biology
Francesco Pastore, Martina Battistoni, Raimondo Sollazzo, Pietro Renna, Fabiola Paciello, Domenica Donatella Li Puma, Eugenio Barone, Onur Dagliyan, Cristian Ripoli, Claudio Grassi
Summary: ADAM10 is a cell surface protease involved in the cleavage of membrane proteins. Dysregulation of ADAM10 has been linked to various pathological conditions, including AD. Researchers have designed a bioengineering strategy to control the cleavage activity of ADAM10, providing insights into AD treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Antonella Tramutola, Simona Lanzillotta, Giuseppe Aceto, Sara Pagnotta, Gabriele Ruffolo, Pierangelo Cifelli, Federico Marini, Cristian Ripoli, Eleonora Palma, Claudio Grassi, Fabio Di Domenico, Marzia Perluigi, Eugenio Barone
Summary: Down syndrome (DS) is associated with Alzheimer's disease (AD) and brain insulin resistance. The KYCCSRK peptide has shown potential for improving insulin signaling in DS and reducing AD-like neuropathology in mice.
Article
Biochemistry & Molecular Biology
Flavia Agata Cimini, Antonella Tramutola, Ilaria Barchetta, Valentina Ceccarelli, Elena Gangitano, Simona Lanzillotta, Chiara Lanzillotta, Maria Gisella Cavallo, Eugenio Barone
Summary: BVRA protein levels can change dynamically in response to insulin and are greater in individuals with lower insulin sensitivity, indicating a correlation with insulin resistance and secretion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Meeting Abstract
Endocrinology & Metabolism
Joao Duarte, Fernanda De Felice, Eugenio Barone, Elizabeth Rhea
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Eugenio Barone
FREE RADICAL BIOLOGY AND MEDICINE
(2022)