Article
Cell Biology
Suwei Chen, Sarah J. Annesley, Rasha A. F. Jasim, Paul R. Fisher
Summary: Studies have shown that oxidative stress and DJ-1 loss are AMPK-dependent and affect mitochondrial respiration and phagocytosis in Dictyostelium cells, ultimately impacting phototaxis, morphogenesis, and growth.
Review
Immunology
Frida Lind-Holm Mogensen, Andrea Scafidi, Aurelie Poli, Alessandro Michelucci
Summary: Microglia are immune cells in the brain that play important roles in immune surveillance and neuroprotection. However, they can also contribute to neuroinflammation and neurotoxicity in neurodegenerative diseases like Parkinson's disease. This review focuses on the role of DJ-1, a protein encoded by the PARK7 gene, in microglia genetic programs and immunological traits. It also discusses the potential of targeting dysregulated pathways in microglia under DJ-1 deficiency as therapeutic approaches for PD, and proposes considering DJ-1 as a biomarker and using DJ-1-enhancing compounds to reduce oxidative stress and neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biochemistry & Molecular Biology
Naouel Gharbi, Dagne Roise, Jorunn-Elise Forre, Amanda J. Edson, Helena A. Hushagen, Valentina Tronci, Ann-Kristin Froyset, Kari E. Fladmark
Summary: The redox-sensitive protein DJ-1 is essential in protecting the retina from oxidative stress, with its absence leading to age-dependent degenerative changes. Restoration of DJ-1 expression in Muller cells inhibits the degenerative phenotype, highlighting the key role of Muller cell DJ-1 in protecting the retina from oxidative stress associated with aging.
Article
Biochemistry & Molecular Biology
Margarida Neves, Mario Graos, Sandra Anjo, Bruno Manadas
Summary: Efforts have been made to understand the physiological and pathological role of DJ-1, a Parkinson's disease (PD) associated protein, to provide new insights into PD pathophysiology. DJ-1 has been found to play several neuroprotective roles, with its ability to modulate signaling pathways being of utmost importance for cell death regulation. The most relevant findings regarding DJ-1's regulatory activity on signaling cascades, including ERK1/2, PI3K/Akt, ASK1, Nrf2, and p53 pathways, have been presented.
Article
Biochemistry & Molecular Biology
James N. N. Tsoporis, Hajera Amatullah, Sahil Gupta, Shehla Izhar, Amin M. M. Ektesabi, Chirag M. M. Vaswani, Jean-Francois Desjardins, Golam Kabir, Ana Paula Teixera Monteiro, Amir K. K. Varkouhi, Nikolaos Kavantzas, Vasileios Salpeas, Ioannis Rizos, John C. C. Marshall, Thomas G. G. Parker, Howard Leong-Poi, Claudia C. C. dos Santos
Summary: Oxidative stress is an early contributor to sepsis-induced myocardial depression, and DJ-1 plays a role as an antioxidant. DJ-1 deficiency improves survival and bacterial clearance in sepsis. This study investigates the role of DJ-1 in sepsis-induced myocardial depression and suggests DJ-1 as a potential therapeutic target.
Article
Pharmacology & Pharmacy
Rania Z. ElGamal, Mariane G. Tadros, Esther T. Menze
Summary: This study evaluates the neuroprotective effects of the DPP4 inhibitor linagliptin in a rotenone-induced rat model of Parkinson's disease. The results show that linagliptin can prevent motor deficits and tissue damage caused by rotenone through anti-inflammatory, anti-apoptotic, and antioxidant mechanisms.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Shiyi Liu, Sheng Xu, Song Liu, Heping Chen
Summary: Autophagy is a highly conserved biological process activated by various external stimuli, and it plays a crucial role in preserving cellular homeostasis and regulating metabolism. DJ-1, a multifunctional protein, is not only a sensor for oxidative stress but also involved in the regulation of autophagy, especially through the oxidative stress response. DJ-1-regulated autophagy has implications in cancer progression, and it could also alleviate neurodegenerative diseases and defective reperfusion diseases. Exploring the regulation of autophagy by DJ-1 provides new avenues for future disease treatment.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Article
Biochemistry & Molecular Biology
Sanghamitra Bhattacharyya, Johnathon Sturgis, Arvydas Maminishkis, Sheldon S. Miller, Vera L. Bonilha
Summary: This study analyzed the impact of DJ-1 expression changes and oxidation of its C residues on RPE function. The results showed that decreased levels of endogenous DJ-1 resulted in increased levels of ROS, morphological changes in mitochondria structure, decreased mitochondrial membrane potential, and decreased viability of RPE cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Domonkos Pap, Apor Veres-Szekely, Beata Szebeni, Adam Vannay
Summary: Inflammatory gastrointestinal diseases are closely related to neurodegenerative diseases such as Parkinson's and Alzheimer's. PARK7/DJ-1 plays a crucial role in maintaining gut microbiome and regulating intestinal inflammation, suggesting it as a potential therapeutic target for gut and brain diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shunya Sasaki, Maaya Nishiko, Takuma Sakamoto, Michael R. Kanost, Hiroko Tabunoki
Summary: The DJ-1 gene is highly conserved in insects, such as Tribolium castaneum, and plays an important role in antioxidative stress mechanisms. TcDJ-1 exhibits higher mRNA expression levels during early pupal and adult stages and knockout leads to increased sensitivity to oxidative stress.
Article
Biochemistry & Molecular Biology
Ramona D'Amico, Enrico Gugliandolo, Rosalba Siracusa, Marika Cordaro, Tiziana Genovese, Alessio Filippo Peritore, Rosalia Crupi, Livia Interdonato, Davide Di Paola, Salvatore Cuzzocrea, Roberta Fusco, Daniela Impellizzeri, Rosanna Di Paola
Summary: Exposure to endocrine disruptors (EDs) may worsen the progression of Parkinson's disease, leading to neuroinflammation and oxidative stress. Additionally, ED exposure can cause changes in behavior and cognition, with a more significant impact observed with exposure to herbicides.
Review
Cell Biology
Pauline Mencke, Ibrahim Boussaad, Chiara D. Romano, Toshimori Kitami, Carole L. Linster, Rejko Kruger
Summary: DJ-1 is a multifunctional protein associated with pathomechanisms of various chronic diseases, with increasing evidence suggesting its potential role in regulating cellular metabolism. Despite the incomplete understanding of its physiological functions, DJ-1 has been implicated in modulating metabolic pathways. In the context of neurodegenerative diseases like Parkinson's, the metabolic effects of DJ-1 may have significant pathophysiological implications.
Review
Pharmacology & Pharmacy
Yumin Wang, Luyan Gao, Jichao Chen, Qiang Li, Liang Huo, Yanchao Wang, Hongquan Wang, Jichen Du
Summary: Parkinson's disease is a complex neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain. Oxidative stress has been implicated in its pathogenesis, with the transcription factor Nrf2 playing a key role in activating protective genes against oxidative stress. Recent studies have shown that bioactive compounds can activate Nrf2 and ameliorate neurotoxins associated with PD, suggesting a potential therapeutic target for the treatment of the disease.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Raul Sanchez-Lanzas, Jose G. Castano
Summary: Mutations in DJ-1/PARK7 are associated with familial early-onset Parkinson's disease. Some DJ-1 missense mutants are unstable proteins, while others are as stable as the wild type. Certain mutants are associated with mitochondria, and their degradation is regulated by the mitochondrial matrix protease LonP1.
SCIENTIFIC REPORTS
(2021)
Article
Cell Biology
Cristina Solana-Manrique, Francisco Jose Sanz, Isabel Torregrosa, Martina Palomino-Schatzlein, Carolina Hernandez-Oliver, Antonio Pineda-Lucena, Nuria Paricio
Summary: The study investigates metabolic disturbances underlying the pathogenesis of Parkinson's disease (PD) using a Drosophila PD model. Through metabolomic analysis, the study finds that metabolic alterations are associated with PD and could potentially serve as therapeutic targets and biomarkers for the disease.
Article
Cell Biology
Sabrina Robichaud, Garrett Fairman, Viyashini Vijithakumar, Esther Mak, David P. Cook, Alexander R. Pelletier, Sylvain Huard, Barbara C. Vanderhyden, Daniel Figeys, Mathieu Lavallee-Adam, Kristin Baetz, Mireille Ouimet
Summary: The study identified multiple lipid droplet-associated proteins involved in lipophagy in macrophages, highlighting their importance in the process. Targeting these proteins to enhance lipophagy for promoting cholesterol efflux in foam cells may represent a novel therapeutic strategy for atherosclerosis.
Article
Chemistry, Analytical
Xu Zhang, Kai Cheng, Zhibin Ning, Janice Mayne, Krystal Walker, Hao Chi, Charles L. Farnsworth, Kimberly Lee, Daniel Figeys
Summary: This study demonstrates that serial enrichment using motif antibodies can capture peptides containing lysine acetylation, propionylation, and succinylation from human gut microbiome samples, providing a new bioinformatic workflow for the study of lysine acylations in the microbiome. The characterization of modification-specific metaproteomes reveals differential distribution of lysine acylations in microbial species with different metabolic capabilities.
ANALYTICAL CHEMISTRY
(2021)
Article
Gastroenterology & Hepatology
Xu Zhang, Krystal Walker, Janice Mayne, Leyuan Li, Zhibin Ning, Alain Stintzi, Daniel Figeys
Summary: This study developed a rapid method for evaluating the viability of live microbiota in biobanks and found that long-term freezing in deoxygenated glycerol buffer has minimal detrimental effects on the cultivability of fecal microbiota.
Article
Clinical Neurology
Kelly M. Sunderland, Derek Beaton, Stephen R. Arnott, Peter Kleinstiver, Donna Kwan, Jane M. Lawrence-Dewar, Joel Ramirez, Brian Tan, Robert Bartha, Sandra E. Black, Michael Borrie, Donald Brien, Leanne K. Casaubon, Brian C. Coe, Benjamin Cornish, Allison A. Dilliott, Dar Dowlatshahi, Elizabeth Finger, Corinne Fischer, Andrew Frank, Julia Fraser, Morris Freedman, Barry Greenberg, David A. Grimes, Ayman Hassan, Wendy Hatch, Robert A. Hegele, Christopher Hudson, Mandar Jog, Sanjeev Kumar, Anthony Lang, Brian Levine, Wendy Lou, Jennifer Mandzia, Connie Marras, William McIlroy, Manuel Montero-Odasso, David G. Munoz, Douglas P. Munoz, Joseph B. Orange, David S. Park, Stephen H. Pasternak, Frederico Pieruccini-Faria, Tarek K. Rajji, Angela C. Roberts, John F. Robinson, Ekaterina Rogaeva, Demetrios J. Sahlas, Gustavo Saposnik, Christopher J. M. Scott, Dallas Seitz, Christen Shoesmith, Thomas D. L. Steeves, Michael J. Strong, Stephen C. Strother, Richard H. Swartz, Sean Symons, David F. Tang-Wai, Maria Carmela Tartaglia, Angela K. Troyer, John Turnbull, Lorne Zinman, Paula M. McLaughlin, Mario Masellis, Malcolm A. Binns
Summary: This is a multi-site, longitudinal, observational cohort study that aims to understand the impact of neurodegenerative and cerebrovascular diseases on dementia presentation. The study recruited 520 participants with prevalent neurodegenerative and cerebrovascular diseases and comprehensively assessed them. Results showed that the participants were predominantly White males with higher education levels. The data will be shared with the global scientific community to identify markers of disease severity, progression, and therapy targets.
ALZHEIMERS & DEMENTIA
(2023)
Article
Biology
Doo Soon Im, Alvin Joselin, Devon Svoboda, Tesuya Takano, Maxime W. C. Rousseaux, Steve Callaghan, Ruth S. Slack, Shin-ichi Hisanaga, Roger J. Davis, David S. Park, Dianbo Qu
Summary: Our study reveals a critical signaling axis involving Cdk5-JIP1-Itch-Notch1 that plays an important role in the regulation of CNS development. Further investigation into how this pathway integrates with additional pathways regulating axonal growth will enhance our understanding of normal central nervous system development and pathological conditions.
Article
Microbiology
Caitlin M. A. Simopoulos, Zhibin Ning, Leyuan Li, Mona M. Khamis, Xu Zhang, Mathieu Lavallee-Adam, Daniel Figeys
Summary: Metaproteomics is a useful tool for studying microbial communities, but the data acquisition process can be time-consuming and resource-intensive. In this study, the researchers developed a computational framework called MetaProClust-MS1 to prioritize samples for follow-up analysis using tandem mass spectrometry (MS/MS). The framework successfully identified microbial responses and disease diagnostic features in gut microbiome data. The study also demonstrated the potential of MetaProClust-MS1 in clinical settings and large-scale metaproteomic screening.
Article
Microbiology
Zhongzhi Sun, Wenju Wang, Leyuan Li, Xu Zhang, Zhibin Ning, Janice Mayne, Krystal Walker, Alain Stintzi, Daniel Figeysa
Summary: The composition and function of the human gut microbiome are closely related to human health. Sugar substitute sweeteners, as commonly used food additives, have potential impacts on the functionality of the microbiome. This study systematically investigated the responses of the human gut microbiome to commonly used sugar substitute sweeteners and revealed the associations between sweetener properties and metaproteomic responses of individual microbiomes.
MICROBIOLOGY SPECTRUM
(2022)
Review
Nutrition & Dietetics
Kendra Hodgkinson, Faiha El Abbar, Peter Dobranowski, Juliana Manoogian, James Butcher, Daniel Figeys, David Mack, Alain Stintzi
Summary: Butyrate, produced by gut microbiota through fermentation of dietary fiber, serves as a key energy source for colonocytes. It has important roles in gastrointestinal health, impacting both host and microbial functions. Maintaining optimal butyrate levels improves gastrointestinal health by supporting colonocyte function, decreasing inflammation, maintaining the gut barrier, and promoting a healthy microbiome. However, increasing butyrate levels in humans and reversing negative outcomes have yielded mixed results, despite its protective actions in intestinal diseases.
CLINICAL NUTRITION
(2023)
Article
Cell Biology
Bensun C. Fong, Imane Chakroun, Mohamed Ariff Iqbal, Smitha Paul, Joseph Bastasic, Daniel O'Neil, Edward Yakubovich, Anthony T. Bejjani, Nastaran Ahmadi, Anthony Carter, Alysen Clark, Gustavo Leone, David S. Park, Noel Ghanem, Renaud Vandenbosch, Ruth S. Slack
Summary: The Rb/E2F axis is an important regulator of neural stem cell fate, coordinating cell-cycle control with NSC activation and quiescence transitions.
Article
Chemistry, Analytical
Haonan Duan, Kai Cheng, Zhibin Ning, Leyuan Li, Janice Mayne, Zhongzhi Sun, Daniel Figeys
Summary: The human gut microbiome is a complex system consisting of hundreds of species, and metaproteomics is a useful tool for studying their expressed functions. However, many lower abundance species cannot be detected by current metaproteomic techniques, which is a challenge in metaproteomics. In this study, the researchers investigated the minimal abundance of a bacterium in a microbiome that can be detected by shotgun metaproteomics. They found that the number of identified peptides and peptide intensity from a 15N-labeled E. coli were linearly correlated with the spike-in levels, even at low abundances. They also discovered that the match-between-run strategy increased the number of quantified peptides, even for low-abundance species.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Kai Cheng, Zhibin Ning, Leyuan Li, Xu Zhang, Joeselle M. Serrana, Janice Mayne, Daniel Figeys
Summary: The studies of microbial communities have become increasingly important in various fields, and metaproteomics is a powerful tool for interpreting the roles of community members. However, analyzing metaproteomic data sets at the genome resolution is still challenging. In this study, a specially designed tool called MetaLab-MAG was developed for characterizing microbiomes from metagenome-assembled genome databases.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemical Research Methods
Marybeth Creskey, Leyuan Li, Zhibin Ning, Emily E. F. Fekete, Janice Mayne, Krystal Walker, Anna Ampaw, Robert Ben, Xu Zhang, Daniel Figeys
Summary: This study demonstrates that the TMT labeling procedures can be simplified by using pre-aliquoted dry TMT reagents, which achieve high labeling efficiency in both microbiome and mammalian cell line samples. The workflow was successfully applied to analyze 97 samples and consistently revealed microbiome responses. This study supports the use of pre-aliquoted, dried, and stored TMT reagents for robust quantitative proteomics and metaproteomics in high throughput applications.
Article
Biochemical Research Methods
Kai Cheng, Zhibin Ning, Leyuan Li, Xu Zhang, Joeselle M. Serrana, Janice Mayne, Daniel Figeys
Summary: The research on microbial communities has gained attention in agriculture, environment, and human health. Metaproteomics has become a powerful tool to understand the roles of microbes through analyzing their expressed proteins. However, analyzing metaproteomic data at genome resolution is challenging due to the lack of efficient bioinformatics tools. Here, we introduce MetaLab-MAG, a specialized tool for microbiome characterization from metagenome-assembled genomes databases. MetaLab-MAG performs well compared to directly searching the gene catalog protein database, allowing quantification of genome-level microbiota compositions and supporting different quantification strategies. It overcomes the obstacles in metaproteomic data analysis and provides comprehensive information from microbiomes to researchers.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Zhongzhi Sun, Zhibin Ning, Kai Cheng, Haonan Duan, Qing Wu, Janice Mayne, Daniel Figeys
Summary: Metaproteomics studies functional changes in the human gut microbiome and peptide identification is a crucial step in this research. However, the large search space complicates peptide identification methods. This study constructed MetaPep, a core peptide database, and demonstrated its importance for human gut metaproteomics research.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)