Review
Chemistry, Multidisciplinary
Ana B. Caballero, Patrick Gamez
Summary: The generation of highly organized amyloid fibrils is associated with a wide range of conformational pathologies, primarily neurodegenerative diseases. Recent findings suggest that impairment in proteostasis network may lead to accumulation and spread of amyloids, contributing to a new focus in anti-amyloid drug design. Chaperones, as known regulators of proteostasis, represent interesting targets for the development of novel therapeutics, with the concept of nanochaperone potentially leading towards the development of cost-effective, disease-modifying drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biology
Mariana Lizardo, Rui Miguel Magalhaes, Freni Kekhasharu Tavaria
Summary: The use of probiotics can improve skin conditions by competing for adhesion sites with pathogenic bacteria, inhibiting their invasion and adhesion, and preventing colonization. Recent studies have shown that probiotics can effectively improve various skin disorders such as atopic dermatitis, acne, eczema, and psoriasis.
Article
Biochemistry & Molecular Biology
Syed Moasfar Ali, Faisal Nabi, Mohammad Furkan, Malik Hisamuddin, Sadia Malik, Syed Mohammad Zakariya, Irum Rizvi, Vladimir N. Uversky, Rizwan H. Khan
Summary: Protein misfolding and amyloid fibril formation are linked to various conformational diseases. Luteolin, a natural flavonoid, has been found to inhibit the aggregation of human insulin, indicating its potential therapeutic role in neuroinflammation. Molecular simulation and spectroscopic techniques confirmed the inhibitory effect of luteolin on the aggregation process.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Tao Zhong, Xiaofan Wu, Wei Xie, Xiangrui Luo, Ting Song, Shuang Sun, Youguang Luo, Dengwen Li, Min Liu, Songbo Xie, Jun Zhou
Summary: ENKD1 is identified as a critical regulator of epidermal stratification by modulating the cell-division orientation of basal keratinocytes and promoting astral microtubule stability. Depletion of ENKD1 leads to thinner epidermis and defective spindle orientation, which can be rescued by introducing the microtubule-binding domain of ENKD1.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Biochemical Research Methods
Casimir Bamberger, Jolene Diedrich, Salvador Martinez-Bartholome, John R. Yates
Summary: This study used a novel high-throughput mass spectrometric method to indirectly measure the accessibility of lysine ε-amine for chemical modification in the proteome, and determined the changes in the 3D proteome during malignant transformation. The results showed that different tumor genotypes reshape a limited set of effector proteins, and alterations in heat shock proteins are key predictors of anticancer drug efficacy.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Multidisciplinary Sciences
Maxime Belondrade, Simon Nicot, Charly Mayran, Lilian Bruyere-Ostells, Florian Almela, Michele A. Di Bari, Etienne Levavasseur, Joel C. Watts, Chantal Fournier-Wirth, Sylvain Lehmann, Stephane Haik, Romolo Nonno, Daisy Bougard
Summary: This study evaluated the amplification of PrPTSE from human sCJD brain samples in different substrates using PMCA, revealing the potential of bank vole PrP substrate in amplifying all sCJD subtypes. In contrast, PMCA in human PrP substrates led to molecular shifts in PrPTSE, with increased permissiveness of V129 PrP substrate to sCJD prion amplification. The combination of PMCA sensitivities and PrPTSE electrophoretic profiles confirmed the classification of 4 distinct major sCJD prion strains. Additionally, the sensitivity required to detect VV2 sCJD prions in cerebrospinal fluid was achieved.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Priyanka Borah, Airy Sanjeev, Venkata Satish Kumar Mattaparthi
Summary: Parkinson's disease is a common progressive neurodegenerative disorder caused by misfolding and aggregation of alpha-synuclein. Recent research shows that Oleuropein aglycone (OleA) stabilizes the monomeric structure of alpha-synuclein, preventing the formation of toxic aggregates and favoring the growth of stable ones, highlighting a potential therapeutic approach.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Review
Biochemistry & Molecular Biology
Jin-Beom Si, Bokyung Kim, Jin Hae Kim
Summary: TTR is a crucial transporter of thyroid hormone and retinol binding protein in human plasma and cerebrospinal fluid, yet it is also known for its amyloidogenic nature leading to various amyloidoses. Research has shown that decreased stability of TTR's native tetrameric conformation is the main cause of these diseases, and recent multidisciplinary investigations have shed light on the mechanistic details of TTR amyloidogenic transformation. Special emphasis has been placed on identifying novel structural features in amyloidogenic species of TTR and discussing the proteolysis-induced fragmentation mechanism that promotes TTR amyloidosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Silvia Errico, Hassan Ramshini, Claudia Capitini, Claudio Canale, Martina Spaziano, Denise Barbut, Martino Calamai, Michael Zasloff, Reinier Oropesa-Nunez, Michele Vendruscolo, Fabrizio Chiti
Summary: The study found that toxic oligomers have a significantly higher affinity for lipid membranes compared to non-toxic oligomers, and that the composition of lipid membranes can modulate the affinity of oligomers for the membranes.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Minoo Qafary, Khosro Khajeh, Matteo Ramazzotti, Ali Akbar Moosavi-Movahedi, Fabrizio Chiti
Summary: A novel lipase from Pseudomonas sp. with high aggregation propensity was studied to elucidate its physicochemical and structural determinants. Amyloid-like structures were found to form at high concentrations, while stable structures were observed in the absence of typical sequence characteristics.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Lenka Hromadkova, Chae Kim, Tracy Haldiman, Lihua Peng, Xiongwei Zhu, Mark Cohen, Rohan de Silva, Jiri G. Safar
Summary: This study aimed to investigate the impact of different mutated tau conformers on the phenotypic variations of Alzheimer's disease (AD) and synaptic loss. By inoculating structurally-characterized Sarkosyl-insoluble tau isolates from AD cases into wild-type mouse neurons, it was found that different mutated tau conformers induced aggregation at different rates and exhibited distinct conformational characteristics in mature neurons. The correlation between the formation of mutated tau aggregates and synaptic loss further confirmed the presence of diverse mutated tau aggregates with different synaptic interactors.
CELL AND BIOSCIENCE
(2023)
Article
Multidisciplinary Sciences
Sarah M. Fantin, Kristine F. Parson, Pramod Yadav, Brock Juliano, Geoffrey C. Li, Charles R. Sanders, Melanie D. Ohi, Brandon T. Ruotolo
Summary: Peripheral myelin protein (PMP22) misfolding is identified as a key factor in various peripheral neuropathies. Mutant forms of PMP22 exhibit differences in stability and propensity to form homodimeric complexes compared to wild-type protein. The formation of PMP22 dimers from destabilized monomers is proposed as a key element in PMP22 mistrafficking, based on combined findings from native ion mobility-mass spectrometry and cellular data.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Hao Li, Nannan Li, Yingqi Tang, Jin Yong Lee
Summary: The study reveals the significant impact of histidine tautomerism on the structure and aggregation tendency of tau protein, promoting the formation of NFTs. This suggests that the histidine tautomerism hypothesis may contribute to the misfolding of tau protein.
ACS CHEMICAL NEUROSCIENCE
(2021)
Review
Cell Biology
Alessandra Bigi, Roberta Cascella, Cristina Cecchi
Summary: The misfolding and aggregation of a-synuclein is the key feature of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies. Soluble oligomeric assemblies formed during the early stages of aggregation are toxic to neurons, while fibrillar conformers contribute to the spreading of the pathology. Recent studies have also shown that a-synuclein fibrils release soluble and highly toxic oligomeric species, leading to immediate dysfunction in recipient neurons. This review discusses the mechanisms of cellular dysfunction caused by a-synuclein oligomers and fibrils in synucleinopathies.
NEURAL REGENERATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Kyung-Ha Lee, Hwan-Kwon Do, Do-Yeon Kim, Wanil Kim
Summary: Chlorogenic acid is a polyphenol found in human diet that impacts human cells, promoting procollagen type I production and skin barrier gene expression. It can be used to restore impaired dermal matrix network and epidermal skin barrier.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Dermatology
Avinash Padhi, Ankit Srivastava, Abarajitha Ramesh, Marcus Ehrstrom, Michel Simon, Eniko Sonkoly, Liv Eidsmo, Peter Bergman, Josefin Lysell
Summary: Increased presence of IL-22(+) cells in the skin is a characteristic finding in skin barrier defects. In this study, reduced levels of peptidylarginine deiminase 1, an enzyme that converts peptidylarginine into citrulline, were observed in lesional psoriatic skin. IL-22 signaling was shown to suppress the expression of peptidylarginine deiminase 1 in epidermal keratinocytes, leading to a decrease in deimination of important proteins for epidermal differentiation. Vitamin D and acitretin partially restored the defect caused by IL-22. These findings identify a potential target for treatment of skin barrier defects.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sara Gouarderes, Aurelie Marches, Patricia Vicendo, Isabelle Fourquaux, Michel Simon, Nofel Merbahi, Laure Gibot
Summary: This study assessed the potential of direct CAP to remodel skin collagens, finding no significant changes in cell viability, pro-collagen I secretion, matrix metalloproteinases activity, and hydroxyproline content after treatment. The plasma-activated culture medium was shown to induce cell apoptosis and growth delay.
BIOELECTROCHEMISTRY
(2022)
Letter
Dermatology
Jon Erik Fraes Diernaes, Charles B. Kromann, Mikkel Boel, Anette Bygum, Gregor Borut Ernst Jemec
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
(2022)
Article
Medicine, General & Internal
Jakob Lillemoen Drivenes, Martin Berg-Jensen, Anette Bygum
Summary: This article presents a case of phototoxic reaction following topical use of NSAID, which was initially mistaken for cellulitis and treated incorrectly, resulting in an exanthematous drug eruption. The patient was subsequently treated with topical and oral medications, but developed post-inflammatory hypopigmentation.
CLINICAL CASE REPORTS
(2022)
Review
Dermatology
E. Cuperus, A. Bygum, L. Boeckmann, C. Bodemer, M. C. Bolling, M. Caproni, A. Diociaiuti, S. Emmert, J. Fischer, A. Gostynski, S. Guez, M. E. van Gijn, K. Hannulla-Jouppi, C. Has, A. Hernandez-Martin, A. E. Martinez, J. Mazereeuw-Hautier, M. Medvecz, I. Neri, V. Sigurdsson, K. Suessmuth, H. Traupe, V. Oji, S. G. M. A. Pasmans
Summary: The broad differential diagnosis of neonatal erythroderma is a diagnostic challenge. Early recognition of the underlying cause is crucial for better treatment and prognosis. Based on the study of 74 cases, a 6-step diagnostic flowchart for neonatal erythroderma is proposed.
JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
(2022)
Article
Genetics & Heredity
Paola Palao-Ocharan, Nieves Prior, Elia Perez-Fernandez, Magdalena Caminoa, DV-HAE-QoL Study Group, Teresa Caballero
Summary: This study validates the use of SF-36v2 for assessing health related quality of life in adult patients with C1-INH-HAE. The results show good internal consistency, construct validity, and test-retest reliability of SF-36v2. Although there are some limitations in content validity, this questionnaire is a useful tool for evaluating the HRQoL of C1-INH-HAE patients.
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Review
Immunology
Anouk E. M. Nouwen, Renske Schappin, N. Tan Nguyen, Aviel Ragamin, Anette Bygum, Christine Bodemer, Virgil A. S. H. Dalm, Suzanne G. M. A. Pasmans
Summary: Comel-Netherton syndrome (NS) is a rare disease caused by genetic variants in the SPINK5 gene, resulting in severe skin barrier impairment and inflammation. This systematic review aimed to provide an overview of systemic treatment options and their outcomes in individuals with NS. A total of 36 case series and case reports were included, describing the effects of 15 different systemic therapies in 48 patients. Treatment options included retinoids, prednisolone, cyclosporine, immunoglobulins, and biologicals. Overall, immunoglobulins and biologicals showed the most promising results in improving the skin condition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Dermatology
Julie Briot, Eric Arbey, Dominique Goudouneche, Dominique Bernard, Michel Simon, Marie-Claire Mechin
Summary: The absence of a functional proteasome in the suprabasal layers of the epidermis causes keratosis linearis with ichthyosis congenita and sclerosing keratoderma syndrome. Inhibited proteasome proteolytic activity leads to down-regulation of filaggrin expression and perturbation of urocanic acid and pyrrolidone carboxylic acid production. Accumulation of small cytoplasmic vesicles and activation of autophagy markers were observed upon proteasome inhibition.
EXPERIMENTAL DERMATOLOGY
(2023)
Editorial Material
Dermatology
Nathalie Jonca, Michel Simon
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Josquin Courte, Ngoc Anh Le, Teng Pan, Luc Bousset, Ronald Melki, Catherine Villard, Jean-Michel Peyrin
Summary: This study demonstrates the limited spreading of preformed aSyn aggregates and suggests that it occurs through molecular sieving of large aSyn seeds. The research also shows that synaptic connections do not facilitate this process. The development of a new microfluidic platform allows for the reconstruction of fully oriented neuronal networks in vitro, enabling the quantification of fluorescent aSyn aggregates spreading between neurons.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Genetics & Heredity
S. B. Gram, J. Bjerrelund, A. M. Jelsig, A. Bygum, C. Leboeuf-Yde, L. B. Ousager
Summary: This systematic review found a lack of well-designed studies on the association between PPPK1 and malignancy. Based on the present literature, no confirmed association was found, questioning the need for surveillance for malignancies in patients with PPPK1.
ORPHANET JOURNAL OF RARE DISEASES
(2023)
Review
Biology
Marie-Claire Mechin, Michel Simon
Summary: This article discusses the role of peptidylarginine deiminases (PADs) in physiological processes and their involvement in human diseases. PAD1 and PAD3 are important for keratinocyte differentiation and epidermal barrier function, while mutations in the PADI3 gene are associated with hair disorders and alopecia. The study highlights the significance of PADs in skin health and disease.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Cell Biology
Adebayo Candide Alioli, Julie Briot, Carole Pons, Hang Yang, Marie Gairin, Dominique Goudouneche, Laura Cau, Michel Simon, Marie-Claire Mechin
Summary: Deimination is a post-translational modification process that converts arginine residues into citrulline. It is controlled by a group of enzymes called peptidylarginine deiminases (PADs). PAD1, one of the enzymes, plays a crucial role in the differentiation of keratinocytes in the human skin. When the expression of PAD1 was down-regulated, it resulted in disrupted differentiation, reduced corneocyte layers, down-regulated expression of important proteins, and altered epidermal permeability.
CELL DEATH DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Tatiana Lupasco, Zhiguo He, Myriam Cassagne, Tomy Sagnial, Lise Brion, Pierre Fournie, Philippe Gain, Gilles Thuret, Michele Allouche, Francois Malecaze, Michel Simon, Stephane D. Galiacy
Summary: The study found that there is a downregulation of gene expression related to mechanical resistance and oxidative stress pathways in early keratoconus samples. Expression of SPRR2A and HMOX1 is also reduced in advanced keratoconus samples. Additionally, there is a decreased expression of KRT16 and KRT14 proteins, as well as differential localization of involucrin protein. Furthermore, immunofluorescence staining for the active form of NRF2 is reduced in keratoconus epithelia compared to controls.
Article
Allergy
Anna Kychygina, Myriam Cassagne, Marie Tauber, Stephane Galiacy, Carle Paul, Pierre Fournie, Michel Simon
Summary: Dupilumab is a new biological therapy for atopic diseases, which has shown effectiveness in treating atopic dermatitis, asthma, and chronic rhinosinusitis. However, it is associated with various adverse events including injection-site reactions, ophthalmic complications, dermatitis, psoriatic lesions, lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. The molecular origin of these adverse events is unclear and further research is needed.
CLINICAL REVIEWS IN ALLERGY & IMMUNOLOGY
(2022)