Article
Biochemistry & Molecular Biology
Rui Jia, Juan S. Bonifacino
Summary: The ubiquitination of LC3B is reversed by the deubiquitinating enzyme USP10, thereby controlling the levels of LC3B and autophagic activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Paivi Yla-Anttila, Soham Gupta, Maria G. Masucci
Summary: Macroautophagy plays a critical role in controlling viral infections, with viruses evolving strategies to interfere with this process. The Epstein-Barr virus-encoded BPLF1 protein regulates selective autophagy, promoting infection and viral production by targeting the cellular defense mechanism.
Article
Cell Biology
Reo Kurusu, Yuki Fujimoto, Hideaki Morishita, Daisuke Noshiro, Shuhei Takada, Koji Yamano, Hideaki Tanaka, Ritsuko Arai, Shun Kageyama, Tomoko Funakoshi, Satoko Komatsu-Hirota, Hikari Taka, Saiko Kazuno, Yoshiki Miura, Masato Koike, Toshifumi Wakai, Satoshi Waguri, Nobuo N. Noda, Masaaki Komatsu
Summary: In addition to membranous organelles, autophagy selectively degrades p62 bodies, including the cargo vault, to prevent diseases such as cancer. The study established a purification method for p62 bodies using human cell lines and identified vault as a constituent using mass spectrometry. The major vault protein directly interacts with NBR1 to recruit vault into p62 bodies, facilitating their efficient degradation.
DEVELOPMENTAL CELL
(2023)
Article
Biochemistry & Molecular Biology
Evelina Valionyte, Yi Yang, Sophie A. Griffiths, Amelia T. Bone, Elizabeth R. Barrow, Vikram Sharma, Boxun Lu, Shouqing Luo
Summary: Inflammatory toxicity selectively blocks p62-droplet formation by inducing caspase-6 cleavage of p62 at a novel site. The N-terminal caspase-6 cleavage product of p62 inhibits droplet formation dominantly, leading to attenuated autophagosome formation dependent on p62 droplets.
CELL DEATH AND DIFFERENTIATION
(2022)
Review
Immunology
Yuhao Zhou, Shucheng Hua, Lei Song
Summary: As a multifunctional protein, p62/SQSTM1 is highly conserved and plays a crucial role in selective autophagy. Recent research has shown its importance in eradicating intracellular bacteria through xenophagy. This review highlights the various roles of p62 in bacterial infections, including antibacterial and infection-promoting aspects, as well as its dependence on xenophagy and independent functions. It also discusses potential therapeutic applications targeting the p62-mediated xenophagy mechanism and unresolved questions regarding p62's roles in bacterial infections.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Yaoxing Wu, Tao Zhou, Jiajia Hu, Yishan Liu, Shouheng Jin, Jianfeng Wu, Xiangdong Guan, Jun Cui
Summary: This study revealed the mechanism of autophagic degradation of dengue virus capsid protein and the role of p62 in this process. The association between p62 and viral capsid protein was dependent on the ubiquitin-binding domain of p62, and poly-ubiquitin conjugated at lysine 76 of capsid protein served as a recognition signal. p62 deficiency led to enhanced dengue virus replication.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Cell Biology
Jia Li, Yanrong Zhou, Wenkai Zhao, Jiao Liu, Rizwan Ullah, Puxian Fang, Liurong Fang, Shaobo Xiao
Summary: This study reveals that DDX10 expression has a significant effect against PRRSV, while its reduction promotes PRRSV proliferation. DDX10 exerts its antiviral effect by regulating type I interferon production. PRRSV infection induces the translocation of DDX10 from the nucleus to the cytoplasm and blocks its antiviral effect through selective autophagy.
Article
Biochemistry & Molecular Biology
Xue Huang, Jia Yao, Lu Liu, Jing Chen, Ligang Mei, Jingjing Huangfu, Dong Luo, Xinyi Wang, Changhai Lin, Xiaorong Chen, Yi Yang, Sheng Ouyang, Fujing Wei, Zhuolin Wang, Shaolin Zhang, Tingxiu Xiang, Dante Neculai, Qiming Sun, Eryan Kong, Edward W. Tate, Aimin Yang
Summary: p62 undergoes reversible S-acylation, which enhances its affinity for autophagic membranes and promotes efficient autophagic degradation of p62-cargo complexes. Increasing p62 acylation accelerates p62 degradation and autophagic clearance of ubiquitinated proteins.
Article
Biochemistry & Molecular Biology
Bin Lv, Yida Pan, Daisen Hou, Ping Chen, Jun Zhang, Yiwei Chu, Mingqi Li, Yan Zeng, Dongqin Yang, Jie Liu
Summary: This study found that ring finger protein 4 (RNF4) is essential for the growth of hepatocellular carcinoma (HCC). Silencing RNF4 suppressed HCC cell growth, induced apoptosis, increased DNA damage, and enhanced sensitivity to DNA damage drugs and radiation. These findings suggest that RNF4 may serve as a novel target for suppressing HCC growth and improving the efficacy of DNA damage therapeutic agents.
Article
Cell & Tissue Engineering
Sharon Russo, Federica Scotto di Carlo, Antonio Maurizi, Giorgio Fortunato, Anna Teti, Danilo Licastro, Carmine Settembre, Tommaso Mello, Fernando Gianfrancesco
Summary: This study describes the establishment of a Zfp687 knock-in mouse model that recapitulates the Paget's disease (PDB) phenotype, leading to significantly altered bone remodeling. The mutation is associated with osteolytic phase, disrupted osteoblast activity, and the presence of woven bone, consistent with the PDB phenotype. Moreover, the study also reveals a link between osteoarthritis and PDB in this mouse model and highlights the oncogenic potential of ZNF687.
Article
Immunology
Sameh S. Zaghlool, Nashwa Abdelaal, Ehab A. M. El-Shoura, Nesreen I. Mahmoud, Yasmin M. Ahmed
Summary: This study found that sulforaphane (SFN) has a protective effect against folic acid-induced acute renal injury through its antioxidant, anti-inflammatory, and anti-apoptotic activities, thus providing a potential therapeutic strategy for preventing such injury.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andre L. Teixeira, Nelson A. Alves
Summary: The UBA domain plays a crucial role in ubiquitin-mediated proteolysis by tagging proteins for degradation. Despite small structural variability among UBA domains, mutations in the conserved hydrophobic patch can lead to conformational instabilities. Investigation on the stability of the p62-UBA domain under different conditions showed negligible effects on its three-helix bundle fold.
JOURNAL OF MOLECULAR MODELING
(2021)
Article
Neurosciences
Benjamin G. Trist, Jennifer A. Fifita, Alison Hogan, Natalie Grima, Bradley Smith, Claire Troakes, Caroline Vance, Christopher Shaw, Safa Al-Sarraj, Ian P. Blair, Kay L. Double
Summary: Multiple neurotoxic proteinopathies co-exist in vulnerable neuronal populations in neurodegenerative diseases, and the interactions between these pathologies may modulate disease progression and serve as targets for disease-modifying treatments. The interactions between superoxide dismutase 1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and ubiquitin-binding protein 62/sequestosome 1 (p62) proteinopathies have been reported in animal models of amyotrophic lateral sclerosis (ALS), but have not been studied in patient tissues. In this study, the spatial relationships between SOD1, TDP-43, and p62 pathologies were explored in post-mortem spinal cord motor neurons of ALS patients, revealing co-deposition and subcellular mislocalization patterns associated with SOD1 gene status. These findings suggest that interactions between these proteins are likely to modulate the formation of their respective proteinopathies and the rate of motor neuron degeneration in ALS patients.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2022)
Review
Neurosciences
Jennilee M. Davidson, Roger S. Chung, Albert Lee
Summary: Investigations into the pathogenetic mechanisms of ALS and FTD have revealed shared dysregulated signaling pathways, with p62 playing a crucial role.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Multidisciplinary Sciences
Yuqing Li, Weijian Chen, Kazumi Ogawa, Masashi Koide, Tadahisa Takahashi, Yoshihiro Hagiwara, Eiji Itoi, Toshimi Aizawa, Masahiro Tsuchiya, Rumiko Izumi, Naoki Suzuki, Masashi Aoki, Makoto Kanzaki
Summary: This study describes the establishment of a feeder-supported in vitro exercise model to study the contractile activity of skeletal muscles. The researchers successfully generated contractile myotubes in this model and found that sIBM patients' myotubes may exhibit abnormal cytoplasmic TDP-43 accumulation during contraction. This model provides a better way to evaluate the exercise-dependent properties of patient muscle cells.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Saeed Akhtar, Ramachandran Samivel, Adrian Smedowski, Aljoharah Alkanaan, Ali Masmali, Omar Kirat, Adnan Ali Khan, Turki Almubrad
Summary: This study identified a unique structure called PENL at the anterior side of the endothelium of the posterior peripheral cornea, which contains unique fibrillar structures unseen in the corneal stroma. This structure may have distinct functions compared to other regions of the cornea.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Angelica Varesi, Lucrezia Irene Maria Campagnoli, Foroogh Fahmideh, Elisa Pierella, Marcello Romeo, Giovanni Ricevuti, Marchesi Nicoletta, Salvatore Chirumbolo, Alessia Pascale
Summary: The bidirectional interaction between the gut microbiota and the Central Nervous System has a significant impact on brain function and the development of neurodegenerative diseases, such as Parkinson's disease. Several studies have explored the role of dysbiosis and intestinal permeability in the onset and progression of Parkinson's disease, but the therapeutic applications of GM modifying approaches need further elucidation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Lucrezia Irene Maria Campagnoli, Nicoletta Marchesi, Mariapia Vairetti, Alessia Pascale, Andrea Ferrigno, Annalisa Barbieri
Summary: Aging is a natural process that leads to physiological changes and increases the vulnerability to diseases. Alterations in gut microbiota composition during aging play a role in liver diseases, such as NAFLD. Restoring a healthy gut microbiota through the use of probiotics may provide a complementary approach to treat NAFLD and other age-related disorders.
Article
Neurosciences
Katarzyna Pawletko, Halina Jedrzejowska-Szypulka, Katarzyna Bogus, Alessia Pascale, Foroogh Fahmideh, Nicoletta Marchesi, Aniela Grajoszek, Edyta Olakowska, Jaroslaw Jerzy Barski
Summary: The study aims to improve the thromboembolic stroke model in rats by using motor tests and following the 3R principles. Additional modifications were made to minimize pain and stress in the animal stroke model. The proposed model showed high reproducibility and low mortality rates, making it suitable for assessing the efficacy of neuro-regenerative therapies.
Article
Biochemistry & Molecular Biology
Katarzyna Pawletko, Halina Jedrzejowska-Szypulka, Katarzyna Bogus, Alessia Pascale, Foroogh Fahmideh, Nicoletta Marchesi, Aniela Grajoszek, Daria Gendosz de Carrillo, Jaroslaw Jerzy Barski
Summary: Ischemic stroke is a leading cause of adult disability and death worldwide. In this study, a new thromboembolic model was used to induce focal cerebral ischemic stroke in rats. The effects of minocycline treatment on neuronal viability and neurodegeneration after stroke were evaluated. The results showed that minocycline administration increased neuron viability, reduced neurodegeneration, and resulted in a significant decrease in infarct volume. Additionally, motor tests demonstrated that reduced inflammation after minocycline treatment improved motor performance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Andrea Ferrigno, Lucrezia Irene Maria Campagnoli, Annalisa Barbieri, Nicoletta Marchesi, Alessia Pascale, Anna Cleta Croce, Mariapia Vairetti, Laura Giuseppina Di Pasqua
Summary: The endogenous antioxidant defense, regulated by HuR, plays a crucial role in the pathogenesis of NAFLD. HuR controls the stability of MnSOD and HO-1 mRNA, two enzymes that protect liver cells from oxidative damage. In an NAFLD animal model, downregulation of HuR was observed along with reduced expression of MnSOD and HO-1, which correlated with oxidative stress and mitochondrial dysfunction. Targeting HuR could be a potential therapeutic strategy for preventing and treating NAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Anna Pacwa, Joanna Machowicz, Saeed Akhtar, Piotr Rodak, Xiaonan Liu, Marita Pietrucha-Dutczak, Joanna Lewin-Kowalik, Marialaura Amadio, Adrian Smedowski
Summary: This study aimed to evaluate the impact of hur silencing on the age-related degeneration of retinal ganglion cells (RGC) and its neuroprotection capacity in the rat glaucoma model. The results showed that silencing the huR gene led to apoptosis and increased oxidative stress markers in RGC, accelerating their decline in number and function. This confirms the key role of HuR in maintaining cell homeostasis and its involvement in the pathogenesis of glaucoma.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Maija Toppila, Maria Hytti, Eveliina Korhonen, Sofia Ranta-aho, Niina Harju, Markus M. Forsberg, Kai Kaarniranta, Aaro Jalkanen, Anu Kauppinen
Summary: Increased oxidative stress, dysfunctional cellular clearance, and chronic inflammation are associated with age-related macular degeneration (AMD). Inhibition of PROLY-OLIGOPEPTIDASE (PREP) by KYP-2047 has been shown to reduce oxidative stress and inflammation, and clear cellular protein aggregates.
Review
Biochemistry & Molecular Biology
Daniel Jamrozik, Radoslaw Dutczak, Joanna Machowicz, Alicja Wojtyniak, Adrian Smedowski, Marita Pietrucha-Dutczak
Summary: Metallothioneins are metal-rich proteins that play important roles in metal homeostasis and detoxification, as well as protecting cells against oxidative stress and promoting cell survival and differentiation. In the eye, these proteins are vital for protecting neuronal retinal cells and disruption in their expression may contribute to age-related eye diseases. This review emphasizes the potential of metallothioneins as a key component of the retinal neurons' endogenous protection system and discusses their expression changes in common eye diseases, as well as their potential as biomarkers for cancer diagnosis.
Review
Biology
Karolina Polewik, Maciej Kosek, Daniel Jamrozik, Iwona Matuszek, Adrian Smedowski, Joanna Lewin-Kowalik, Marita Pietrucha-Dutczak
Summary: Diabetic retinopathy is a progressive complication of diabetes that can lead to vision loss. Animal models are useful tools for studying the mechanisms and testing new therapeutic strategies for diabetic retinopathy. This review focuses on commonly used rodent models in laboratory practice and provides suggestions for their application and explains their disadvantages. It is hoped that this review will help in selecting appropriate models for studying diabetic retinopathy.
Article
Pharmacology & Pharmacy
Eveliina Korhonen, Niina Piippo, Maria Hytti, Kai Kaarniranta, Anu Kauppinen
Summary: Age-related macular degeneration (AMD) is a common eye disease among the elderly that can cause impaired and irreversible loss of vision. This study suggests that cis-urocanic acid has the potential to protect retinal pigment epithelial cells and prevent inflammation, making it a possible treatment for chronic ocular diseases like AMD.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Nicoletta Marchesi, Pasquale Linciano, Lucrezia Irene Maria Campagnoli, Foroogh Fahmideh, Daniela Rossi, Giosue Costa, Francesca Alessandra Ambrosio, Annalisa Barbieri, Simona Collina, Alessia Pascale
Summary: In this study, the researchers found a strong association between HuD and several nervous system diseases through an interaction network analysis. They focused on the relationship between HuD and BDNF, and discovered that folic acid can regulate BDNF expression by modulating HuD. These findings suggest that BDNF could be a therapeutic target for neurological and psychiatric diseases, and folic acid may act as an epigenetic modulator.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Lucrezia Irene Maria Campagnoli, Angelica Varesi, Annalisa Barbieri, Nicoletta Marchesi, Alessia Pascale
Summary: The human microbiota refers to a diverse range of microorganisms that live in different parts of the human body, including the gut, oral cavity, skin, and eyes. Recent studies have shown that the ocular surface microbiota plays a crucial role in maintaining ocular surface homeostasis and preventing colonization by pathogens. There is also emerging evidence of a potential connection between the gut microbiota and ocular health, with a gut-eye axis being implicated in the pathogenesis of various eye diseases. Understanding this link could lead to the development of new therapeutic approaches for these diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Sonia La Cognata, Donatella Armentano, Nicoletta Marchesi, Pietro Grisoli, Alessia Pascale, Marion Kieffer, Angelo Taglietti, Anthony P. Davis, Valeria Amendola
Summary: This study reports a novel organic cage as a potential antimicrobial and antifungal agent. Experimental results demonstrate that the cage can bind and transport specific anions and exhibit antimicrobial activity against Staphylococcus aureus.
CHEMISTRY-SWITZERLAND
(2022)
Article
Immunology
Anna Pacwa, Joanna Machowicz, Alicja Wojtyniak, Marita Pietrucha-Dutczak, Elisa Toropainen, Ali Koskela, Ewa Mrukwa-Kominek, Joanna Lewin-Kowalik, Adrian Smedowski
Summary: The study evaluated the effect of SCD1 inhibitor MF-438 on the differentiation of monocytes exposed to eye drop detergents. The results showed a strong correlation between SCD1 concentration and macrophage count in the culture.
JOURNAL OF INFLAMMATION RESEARCH
(2022)