Article
Medicine, Legal
Minh-Ha Thi Do, Joy Cavagnaro, Mark Butt, Pramod S. Terse, John C. McKew
Summary: In toxicology studies involving cyclocreatine, a creatine analog, it was found that wild-type mice were more sensitive to cyclocreatine-induced toxicity compared to creatine transporter-deficient mice. The biodistribution study showed greater accumulation of cyclocreatine in the brains of wild-type mice, indicating its ability to be transported by the creatine transporter. Although the transporter-deficient mice appeared to be more sensitive, there were no functional correlates to this sensitivity in the strain.
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2021)
Article
Neurosciences
Enrico Adriano, Annalisa Salis, Gianluca Damonte, Enrico Millo, Maurizio Balestrino
Summary: The study suggests that acute administration of GAA does not have epileptogenic or neurotoxic effects on the brain. Additionally, diacetyl-GAAE improves tissue viability but not through an increase in creatine or phosphocreatine.
Article
Toxicology
Yancy Ferrer-Acosta, Sergio Rodriguez-Masso, Dinely Perez, Vesna A. Eterovic, P. A. Ferchmin, Antonio Henrique Martins
Summary: Memantine has neuroprotective activity through a nicotinic pathway, similar to the nicotinic drug 4R. Its mechanism involves the release of acetylcholine, activation of alpha 4 beta 2 acetylcholine receptors, and is independent of MEK/MAPK signaling.
TOXICOLOGY IN VITRO
(2022)
Article
Biophysics
Shizhe Li, Simona Bianconi, Jan Willem van der Veen, An Dang Do, JoEllyn Stolinski, Kim M. Cecil, Fady Hannah-Shmouni, Forbes D. Porter, Jun Shen
Summary: X-linked creatine transporter deficiency (CTD) is a condition caused by pathogenic variants in the X-linked gene SLC6A8, leading to reduced phosphocreatine and total creatine concentrations. Despite the diminished role of creatine and phosphocreatine in oxidative phosphorylation in CTD, our study found no elevation of lactate or lowered pH, indicating that the brain still largely relies on oxidative metabolism for energy supply. Our results suggest that mitochondrial function could be a potential therapeutic target for CTD.
NMR IN BIOMEDICINE
(2021)
Article
Neurosciences
Aloise Mabondzo, Rania Harati, Lea Broca-Brisson, Anne-Cecile Guyot, Narciso Costa, Francesco Cacciante, Elena Putignano, Laura Baroncelli, Matthew R. Skelton, Cathy Saab, Emmanuelle Martini, Henri Benech, Thomas Joudinaud, Jean-Charles Gaillard, Jean Armengaud, Rifat Hamoudi
Summary: Creatine transporter deficiency (CTD) is a genetic disorder that impairs the uptake of creatine into the brain, leading to intellectual disability. This study investigated the therapeutic potential of dodecyl creatine ester (DCE) in a mouse model of CTD and identified biomarkers associated with cognitive improvement. The findings shed light on the pathogenesis of CTD and provide insights for potential treatments.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Oncology
Raisa I. Krutilina, Hilaire Playa, Danielle L. Brooks, Luciana P. Schwab, Deanna N. Parke, Damilola Oluwalana, Douglas R. Layman, Meiyun Fan, Daniel L. Johnson, Junming Yue, Heather Smallwood, Tiffany N. Seagroves
Summary: This study identified creatine kinase, brain isoform (CKB) as a downstream gene of HIF-1 transcription factor that promotes invasion and metastasis in ER-negative breast cancer. Inhibition of CKB or creatine kinase activity using cCr suppressed cell invasion, invadopodia formation, and lung metastasis. In combination with conventional chemotherapy agents, cCr enhanced growth inhibition. These findings suggest that targeting CKB and cellular metabolism may be effective in treating metastatic breast cancer.
Article
Endocrinology & Metabolism
Adam M. Wawro, Chandresh R. Gajera, Steven A. Baker, Jeffrey J. Nirschl, Hannes Vogel, Thomas J. Montine
Summary: This study conducted a comprehensive investigation on creatine (Cr) transporter deficiency in three ubiquitous Slc6a8 deficient mice, revealing significant differences in organ-specific uptake of Cr-d3, restricted growth except for the brain, progressive vacuolar myopathy, and markedly shortened lifespan in these mice.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Neurosciences
Jiaqing Li, Sanqing Xu
Summary: This case report describes a 3-year-9-month-old boy with GDD, autistic behavior, and epilepsy, who was diagnosed with CTD through MR spectroscopy and metabolic screening. Creatine supplementation therapy led to seizure cessation and modest cognitive improvement after six months of treatment. This highlights the importance of MR spectroscopy and metabolic screening in early diagnosis and therapeutic intervention.
Review
Genetics & Heredity
Elsa Ghirardini, Francesco Calugi, Giulia Sagona, Federica Di Vetta, Martina Palma, Roberta Battini, Giovanni Cioni, Tommaso Pizzorusso, Laura Baroncelli
Summary: CTD is an X-linked metabolic disorder caused by mutations in the SLC6A8 gene, leading to intellectual disability, autistic behavior, and epilepsy. There is no effective treatment for CTD, making research on novel intervention strategies a major scientific challenge. Animal models are crucial for studying the disease mechanisms and developing therapeutics, with rodent models showing promise in recapitulating human CTD phenotypes.
Article
Genetics & Heredity
Myriam Abdennadher, Sara K. Inati, Samar Rahhal, Omar Khan, Luca Bartolini, Audrey Thurm, William Theodore, Judith S. Miller, Forbes D. Porter, Simona Bianconi
Summary: This study reported the seizure characteristics and EEG findings in males with creatine transporter deficiency (CTD). The findings showed that seizures were frequent in the study cohort, but tended to respond to antiseizure medications. Longitudinal follow-up provided further insight into the emergence of seizures and EEG abnormalities, soliciting future studies with long-term follow-up.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Article
Neurosciences
Pablo Vergara, Gabriela Pino, Jorge Vera, Felipe Arancibia, Magdalena Sanhueza
Summary: Prolonged changes in neural activity trigger homeostatic synaptic plasticity, allowing neuronal networks to operate within functional ranges. Deafferentation causes rapid and diverse compensations, which may contribute to understanding homeostatic or pathological events after brain injury.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Elsa Ghirardini, Giulia Sagona, Angel Marquez-Galera, Francesco Calugi, Carmen M. Navarron, Francesco Cacciante, Siwei Chen, Federica Di Vetta, Lorenzo Dada, Raffaele Mazziotti, Leonardo Lupori, Elena Putignano, Pierre Baldi, Jose P. Lopez-Atalaya, Tommaso Pizzorusso, Laura Baroncelli
Summary: This study found that the absence of cellular creatine affects the function of specific neurons, which may be one of the causes of Creatine Transporter Deficiency (CTD). Additionally, the study identified a potential therapeutic approach targeting these neurons to improve CTD symptoms.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yang Liu, Wen Guo, Si-Lu Hong
Summary: This study found that aerobic exercise can improve neuronal apoptosis and spatial memory in aging mice, and its mechanism may be related to the regulation of the DAPK1 pathway.
Review
Nutrition & Dietetics
Xiaoying Cui, Darryl W. Eyles
Summary: This article provides an update on the actions of vitamin D in the brain and the cellular processes it may target in psychiatry and neurology.
Review
Cell Biology
Nhi Thao Tran, Sharmony B. Kelly, Rod J. Snow, David W. Walker, Stacey J. Ellery, Robert Galinsky
Summary: Creatine shows promise as a neuroprotective intervention for HIE, but there are still key knowledge gaps and improvements needed in preclinical studies before it can be considered for human fetal/neonatal neuroprotection trials.
Review
Pharmacology & Pharmacy
Olja Mijanovic, Anastasiia I. Petushkova, Ana Brankovic, Boris Turk, Anna B. Solovieva, Angelina I. Nikitkina, Sergey Bolevich, Peter S. Timashev, Alessandro Parodi, Andrey A. Zamyatnin
Summary: Lysosomal proteases, specifically human cathepsin D, play a crucial role in maintaining cell homeostasis by managing protein turnover. Dysregulation of cathepsin D can contribute to various disorders, such as neurodegenerative diseases and cancer progression. Targeting cathepsin D could provide significant diagnostic benefits and innovative therapeutic approaches.
Article
Oncology
Alessandro Parodi, Dmitry Kostyushev, Sergey Brezgin, Anastasiya Kostyusheva, Tatiana Borodina, Roman Akasov, Anastasia Frolova, Vladimir Chulanov, Andrey A. Zamyatnin Jr
Summary: In order to increase the accumulation of drugs in tumors, various nanocarriers have been designed. The development of biomimetic nanomedicine allows the generation of nanoparticles with the same characteristics as cells that naturally infiltrate tumors. Moreover, strategies such as cell membrane transfer and biomimetic targeting can enhance the targeting efficiency of drugs in tumors.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Cell Biology
Magdalena Rudzinska-Radecka, Anastasia S. Frolova, Anastasia V. Balakireva, Neonila V. Gorokhovets, Vadim S. Pokrovsky, Darina V. Sokolova, Dmitry O. Korolev, Natalia V. Potoldykova, Andrey Z. Vinarov, Alessandro Parodi, Andrey A. Zamyatnin
Summary: This study investigated the expression of CtsB and StfA in renal cell carcinoma (RCC) and found that they are associated with RCC development, with a positive correlation between their expression.
Editorial Material
Pharmacology & Pharmacy
Andrey A. Zamyatnin, Alessandro Parodi
Article
Biotechnology & Applied Microbiology
Ambra Costa, Carolina Balbi, Patrizia Garbati, Maria Elisabetta Federica Palama, Daniele Reverberi, Antonella De Palma, Rossana Rossi, Dario Paladini, Domenico Coviello, Pierangela De Biasio, Davide Ceresa, Paolo Malatesta, Pierluigi Mauri, Rodolfo Quarto, Chiara Gentili, Lucio Barile, Sveva Bollini
Summary: Cardiomyocyte renewal is a clinical need for cardiac regeneration, and stem cell paracrine therapy has been shown to provide cardiac protection and enhance repair. In this study, it was found that extracellular vesicles released by fetal amniotic fluid-derived stem cells could promote cardiomyocyte renewal, possibly through the mediation of factors such as Agrin.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Elena O. Kutumova, Ilya R. Akberdin, Ilya N. Kiselev, Ruslan N. Sharipov, Vera S. Egorova, Anastasiia O. Syrocheva, Alessandro Parodi, Andrey A. Zamyatnin, Fedor A. Kolpakov
Summary: This article introduces the application of nanomedicine in cancer treatment and the role of physiologically based pharmacokinetic modeling in the design and prediction of therapeutic effects of nanocarriers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Alessandro Parodi, Ekaterina P. Kolesova, Maya V. Voronina, Anastasia S. Frolova, Dmitry Kostyushev, Daria B. Trushina, Roman Akasov, Tatiana Pallaeva, Andrey A. Zamyatnin
Summary: Nanomedicine aims to improve current therapies, with a focus on cancer treatment. By enhancing drug targeting and pharmacokinetics properties, it opens up possibilities for new treatment concepts based on physical therapy and biologics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Olja Mijanovic, Aleksandra Jakovleva, Ana Brankovic, Kristina Zdravkova, Milena Pualic, Tatiana A. Belozerskaya, Angelina Nikitkina, Alessandro Parodi, Andrey A. Zamyatnin
Summary: In this review, we summarized the molecular background, involvement in various diseases, and clinical significance for diagnosis and therapy of Cathepsin K (CatK).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Sergey Brezgin, Anastasiya Kostyusheva, Natalia Ponomareva, Ekaterina Bayurova, Alla Kondrashova, Anastasia Frolova, Olga Slatinskaya, Landysh Fatkhutdinova, Georgy Maksimov, Mikhail Zyuzin, Ilya Gordeychuk, Alexander Lukashev, Sergey Makarov, Alexander Ivanov, Andrey A. Zamyatnin Jr, Vladimir Chulanov, Alessandro Parodi, Dmitry Kostyushev
Summary: Biological nanoparticles, such as extracellular vesicles (EVs) and extracellular vesicle-mimetic nanovesicles (EMNVs), have been extensively studied as drug delivery vehicles in medical applications. This study investigated the properties and drug delivery abilities of EVs and EMNVs, and analyzed their use for delivering the chemotherapeutic drug doxorubicin. EMNVs were found to be more effectively internalized, while EVs showed higher intracellular release of doxorubicin.
Review
Biotechnology & Applied Microbiology
Sergey Brezgin, Alessandro Parodi, Anastasiya Kostyusheva, Natalia Ponomareva, Alexander Lukashev, Darina Sokolova, Vadim S. Pokrovsky, Olga Slatinskaya, Georgy Maksimov, Andrey A. Zamyatnin Jr, Vladimir Chulanov, Dmitry Kostyushev
Summary: Extracellular vesicles (EVs), cell-derived biological nanoparticles, have gained significant interest for drug delivery due to their ideal biocompatibility, safety, ability to cross biological barriers, and surface modification potential. However, the translation of EVs into practical applications has been challenging due to issues in up-scaling, synthesis, and quality control methods. Advances in manufacturing technology now allow EVs to carry various therapeutic cargoes, and new technologies have been introduced to improve EV production, isolation, characterization, and standardization.
BIOTECHNOLOGY ADVANCES
(2023)
Article
Biochemistry & Molecular Biology
Ekaterina P. Kolesova, Vera S. Egorova, Anastasiia O. Syrocheva, Anastasiia S. Frolova, Dmitry Kostyushev, Anastasiia Kostyusheva, Sergey Brezgin, Daria B. Trushina, Landysh Fatkhutdinova, Mikhail Zyuzin, Polina A. Demina, Evgeny V. Khaydukov, Andrey A. Zamyatnin, Alessandro Parodi
Summary: Proteolytic activity plays a crucial role in cell homeostasis and function, with implications in cancer progression and treatment response. Endosomes, which are often the final destination of internalized nanoparticles, are major sites of cellular proteolytic activity. However, little is known about the impact of nanoparticles on endosomal biology. In this study, we generated albumin nanoparticles with varying resistance to proteolysis and demonstrated a relationship between their sensitivity to proteases and drug delivery properties, irrespective of the degree of proteolytic degradation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anastasia S. Frolova, Natalia K. Tikhomirova, Igor I. Kireev, Evgeni Yu. Zernii, Alessandro Parodi, Konstantin I. Ivanov, Andrey A. Zamyatnin Jr
Summary: Cysteine cathepsins are important in tumor development and metastasis, and their expression is often increased in tumor cells. This study assessed and compared the expression, localization, and maturation of all eleven cysteine cathepsins in kidney cells and kidney cancer cell lines. The results showed higher expression levels of certain cathepsins in tumor cells, as well as their presence in the nucleus and higher maturation levels compared to embryonic cells. These findings can be used for diagnostic development and investigating cysteine cathepsins as potential therapeutic targets.
BIOCHEMISTRY-MOSCOW
(2023)
Review
Pharmacology & Pharmacy
Vera S. Egorova, Ekaterina P. Kolesova, Manu Lopus, Neng Yan, Alessandro Parodi, Andrey A. Zamyatnin
Summary: Cathepsin B is a lysosomal cysteine protease involved in various cellular processes and its overexpression and activity have been linked to pathological conditions such as cancer. Targeting cathepsin B activity has become a promising strategy for tumor-specific therapy and drug delivery. This review summarizes different technologies designed to improve cancer treatments by responsive to cathepsin B activity, which plays a key role in disease progression and treatment response.
Article
Chemistry, Multidisciplinary
Neng Yan, Yuhuai Wang, Tin Yan Wong, Yubing Hu, Huo Xu, Parodi Alessandro, Ke Pan, Jingjing Liu, Henry Lam, Ben Zhong Tang, Jianbo Shi
Summary: This study prepared aggregation-induced emission fluorogen-incorporated nanoparticles (AIE-NPs) with different surface roughness by exposing the nanoparticles to the human digestive system (HDS) for different durations. The study found that the surface roughness affected the interaction between the nanoparticles and the liver. Additionally, the rougher nanoparticles facilitated cellular internalization and induced lysosomal alkalization, ROS production, and cell apoptosis.
ENVIRONMENTAL SCIENCE-NANO
(2023)
Article
Biochemistry & Molecular Biology
Magdalena Rudzinska, Karolina H. Czarnecka-Chrebelska, Ekaterina B. Kuznetsova, Sofya V. Maryanchik, Alessandro Parodi, Dmitry O. Korolev, Nataliya Potoldykova, Yulia Svetikova, Andrey Z. Vinarov, Marina V. Nemtsova, Andrey A. Zamyatnin
Summary: Long non-coding RNAs (lncRNAs) are specifically expressed in different tissues and cancers, and have been reported to be involved in tumor growth and metastasis by controlling gene expression. PROX1-AS1 expression in renal cell carcinoma (RCC) is associated with tumor progression, with a positive correlation to metastasis, tumor stage, and grade. Global demethylation may significantly increase PROX1-AS1 expression level, potentially making it a new diagnostic marker and therapeutic target for RCC.
