Review
Biochemistry & Molecular Biology
Ayush Ranawade, Rati Sharma, Erel Levine
Summary: The Heat Shock Response (HSR) is a conserved genetic system that protects the proteome in organisms. Mathematical modeling has been crucial in understanding its regulation, but there are still many unanswered questions that can benefit from quantitative modeling.
Review
Cell Biology
Ariadni Androvitsanea, Kostas Stylianou, Eleni Drosataki, Ioannis Petrakis
Summary: Research has shown that heat-shock proteins can have varying effects on the immune system, either triggering immune responses or alleviating them, which is important for studying and treating autoimmune diseases.
Article
Biochemistry & Molecular Biology
Sanduni Wasana Jayaweera, Solmaz Surano, Nina Pettersson, Elvira Oskarsson, Lovisa Lettius, Anna L. Gharibyan, Intissar Anan, Anders Olofsson
Summary: The study demonstrates that TTR can interfere with IAPP amyloid-formation, prolonging the lag-phase and impairing elongation. The interfering ability correlates inversely with the thermodynamic stability of TTR, but not with kinetic stability. TTR's interference ability remains effective in the low pH environment of IAPP-containing granules, but TTR-stabilizing drugs partially weaken its efficacy.
Article
Biochemistry & Molecular Biology
Binyou Wang, Stuart P. Moon, Giuliano Cutolo, Afraah Javed, Benjamin S. Ahn, Andrew H. Ryu, Matthew R. Pratt
Summary: O-GlcNAc modification protects cells against stress-induced cell death by directly inhibiting the apoptotic pathway. The modified chaperone, HSP27, exhibits enhanced antiapoptotic function in an in vitro context. These findings provide molecular insights into how O-GlcNAc serves as a mediator of cellular stress and have important implications for human diseases like cancer and neurodegeneration.
ACS CHEMICAL BIOLOGY
(2023)
Article
Oncology
Rodney H. Falk, Mia Haddad, Crystal R. Walker, Sharmila Dorbala, Sarah A. M. Cuddy
Summary: The study showed that tafamidis therapy significantly increases serum TTR levels in patients with ATTR cardiomyopathy, indicating a stabilizing effect. Changes in TTR levels post-therapy may serve as a surrogate marker for stabilization and a more accurate measure of drug efficacy compared to in vitro tests.
JACC: CARDIOONCOLOGY
(2021)
Review
Chemistry, Applied
Zhiyu Xie, Fantao Sun, Marco Pistolozzi, Jinwu Yan
Summary: Amyloidosis is a rare disorder characterized by the deposition of protein aggregates in body tissues. One common form of amyloidosis is transthyretin amyloidosis (ATTR), which manifests as either a polyneuropathy or a cardiomyopathy. Early detection, diagnosis, and treatment of ATTR are crucial for patient management.
Article
Biochemistry & Molecular Biology
Sabrina Ghosh, Carlos Villacorta-Martin, Jonathan Lindstrom-Vautrin, Devin Kenney, Carly S. Golden, Camille V. Edwards, Vaishali Sanchorawala, Lawreen H. Connors, Richard M. Giadone, George J. Murphy
Summary: In this study, neuronal and cardiac cells were exposed to wild-type and destabilized TTR variants, and transcriptional and epigenetic profiling was performed. The results revealed overlapping and distinct cell type- and amyloidogenic protein-specific signatures in response to different amyloidogenic variants, providing insight into the mechanisms underlying protein-mediated cellular damage and ER stress.
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
(2023)
Article
Biochemistry & Molecular Biology
Elzbieta Wieczorek, Zofia Wygralak, Sylwia Kedracka-Krok, Patrycja Bezara, Dominika Bystranowska, Piotr Dobryszycki, Andrzej Ozyhar
Summary: TTR is a protein that transports thyroid hormones and retinol and functions as a neuro-protective factor and sensor of oxidative stress. This study found that the stability of TTR is influenced by calcium ions and other factors, resulting in the formation of blue autofluorescent compounds. The redox state of TTR affects the dynamics and properties of these compounds.
Review
Clinical Neurology
Antonia Carroll, P. James Dyck, Mamede de Carvalho, Marina Kennerson, Mary M. Reilly, Matthew C. Kiernan, Steve Vucic
Summary: Hereditary transthyretin amyloidosis (ATTRv) is a severe genetic disease that primarily affects the peripheral and autonomic nervous system, heart, kidney, and eyes. Misdiagnosis rates are high, leading to diagnostic delays and increased disability. Timely diagnosis is crucial due to the availability of effective treatments. This review highlights key advances in diagnostic techniques, management strategies, and biomarker development for disease progression in ATTRv.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2022)
Review
Plant Sciences
Yunzhuan Zhou, Fuxiang Xu, Yanan Shao, Junna He
Summary: As global warming intensifies, the earth's average temperature continues to rise. Plants have developed two main mechanisms, the heat stress response and the thermomorphogenesis response, to cope with elevated temperatures. This review summarizes recent progress in understanding these heat-responsive molecular regulatory pathways in plants and discusses future perspectives in this field.
Article
Cardiac & Cardiovascular Systems
Ulrika Thelander, Gunilla T. Westermark, Gunnar Antoni, Sergio Estrada, Alice Zancanaro, Elisabet Ihse, Per Westermark
Summary: This study found that the binding of skeletal probes to amyloid-containing hearts is due to the presence of tiny calcification clusters, which are not directly associated with amyloid fibrils. Therefore, bone scans can be considered surrogate markers of ATTR amyloid, but caution is needed when estimating amyloid load or disease progression.
INTERNATIONAL JOURNAL OF CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tsukumi Miwa, Hideki Taguchi
Summary: Research has shown that IbpA down-regulates the expression of multiple heat shock proteins (Hsps) by repressing the translation of the heat shock transcription factor sigma(32), and plays a crucial role in shutting down the heat shock response. These findings reveal an unknown role of IbpA in regulating the heat shock response at the translational level.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Environmental Sciences
Shao-Shuai Bi, Milton Talukder, Xue-Tong Sun, Mei-Wei Lv, Jing Ge, Cong Zhang, Jin-Long Li
Summary: This study assessed the neurotoxic effects of chronic cadmium (Cd) exposure on the chicken cerebellum and investigated the expression of genes related to the heat-shock response. The results showed that Cd exposure led to clinical symptoms of ataxia in the chickens, decreased the number of Purkinje cells, and induced degeneration of Purkinje cells. Cd exposure also affected the expression of heat-shock factors and proteins. These findings shed light on the toxic effects of Cd on the cerebellum and provide evidence for the health risks posed by Cd exposure.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Review
Oncology
Enzo M. Scutigliani, Yongxin Liang, Hans Crezee, Roland Kanaar, Przemek M. Krawczyk
Summary: Hyperthermia is a method of exposing tumors to elevated temperatures to enhance the effects of chemotherapy and radiotherapy. However, its efficacy is limited by factors such as heat stress response. Targeting this cellular defense mechanism may improve the effectiveness of hyperthermia-based therapies.
Review
Pharmacology & Pharmacy
Ana P. Spencer, Marilia Torrado, Beatriz Custodio, Sara C. Silva-Reis, Sofia D. Santos, Victoria Leiro, Ana P. Pego
Article
Oncology
Christoph Niemietz, Filipa Bezerra, Maria Rosario Almeida, Shuling Guo, Brett P. Monia, Maria Joao Saraiva, Paula Schuetz, Hartmut H-J Schmidt, Andree Zibert
EXPERIMENTAL CELL RESEARCH
(2020)
Article
Immunology
Joao Moreira, Susete Costelha, Margarida Saraiva, Maria Joao Saraiva
Summary: Inflammation is a key feature of neurodegenerative disorders like ATTRv. Compared to wild type animals, chemokine expression is significantly downregulated in the peripheral nervous system of a mouse model of the disease, possibly due to a mechanism that leads to the inactivation of TTR activation in patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Joana Magalhaes, Jessica Eira, Marcia Almeida Liz
Summary: TTR is an extracellular protein involved in transporting thyroxin and retinol, but can also lead to amyloidosis. Recent studies show novel cellular activities of TTR, suggesting potential impacts on brain health, cellular fate, and metabolism beyond its known carrier functions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Neurosciences
Sofia Alcada-Morais, Nelio Goncalves, Veronica Moreno-Juan, Belen Andres, Sofia Ferreira, Joana M. Marques, Joana Magalhaes, Joao M. M. Rocha, Xinli Xu, Matilde Partidario, Rodrigo A. Cunha, Guillermina Lopez-Bendito, Ricardo J. Rodrigues
Summary: The study found that A(2A)R controls the radial migration of cortical projection neurons, not just the tangential migration of somatostatin(+) interneurons. Furthermore, A(2A)R plays a crucial role in the multipolar-bipolar transition and axon formation of the latter.
Article
Biochemistry & Molecular Biology
Filipa Bezerra, Christoph Niemietz, Hartmut H. J. Schmidt, Andree Zibert, Shuling Guo, Brett P. Monia, Paula Goncalves, Maria Joao Saraiva, Maria Rosario Almeida
Summary: The SerpinA1 plays an important role in regulating the proteolysis and aggregation of transthyretin. Downregulation of SerpinA1 leads to increased TTR levels in mice plasma and deposition in the cardiac tissue.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Joana Magalhaes, Emilie Tresse, Patrick Ejlerskov, Erling Hu, Yawei Liu, Andrea Marin, Alexia Montalant, Letizia Satriano, Carsten Friis Rundsten, Eva Maria Meier Carlsen, Rasmus Rydbirk, Ali Sharifi-Zarchi, Jesper Boje Andersen, Susana Aznar, Tomasz Brudek, Konstantin Khodosevich, Marco Prinz, Jean-Francois Marie Perrier, Manu Sharma, Thomas Gasser, Shohreh Issazadeh-Navikas
Summary: Familial Parkinson disease (PD) is associated with rare genetic mutations, however, most patients with sporadic (s)PD have largely unknown etiology and poorly characterized basis for progression to dementia (sPDD). Loss of IFN beta or IFNAR1 causes pathological and behavioral changes resembling PDD, suggesting dysregulated genes in the IFN beta-IFNAR signaling pathway may predispose to sPD. Transcriptomic analysis revealed defective neuronal IFN beta-IFNAR signaling, with elevated PIAS2 expression associated with sPDD. Meta-analysis of GWASs identified sequence variants in IFN beta-IFNAR-related genes in sPD patients, while sPDD patients showed higher levels of PIAS2 mRNA and protein in neurons.
MOLECULAR PSYCHIATRY
(2021)
Article
Multidisciplinary Sciences
Aubin Michalon, Andreas Hagenbuch, Christian Huy, Evita Varela, Benoit Combaluzier, Thibaud Damy, Ole B. Suhr, Maria J. Saraiva, Christoph Hock, Roger M. Nitsch, Jan Grimm
Summary: Through analyzing memory B cell repertoires of healthy elderly, researchers developed a selective human antibody that removes cardiac amyloid by recruiting phagocytic immune cells.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Maurizio Gulino, Sofia Duque Santos, Ana Paula Pego
Summary: Platinum nanoparticles (PtNPs) have diverse applications in medicine, including drug delivery and surface coating on biomedical devices. Studies show that PtNPs have limited impact on cell viability in normal conditions and do not exacerbate tissue responses under neuropathological induced scenarios. However, PtNPs can cause microglial cell activation and morphological alterations in certain brain regions. Further research is needed to ensure the safe use of PtNPs and develop more biocompatible nanoparticles for brain applications.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Cell Biology
Jessica Eira, Joana Magalhaes, Nidia Macedo, Maria Elena Pero, Thomas Misgeld, Monica M. Sousa, Francesca Bartolini, Marcia A. Liz
Summary: TTR plays a role in promoting axon elongation by modulating microtubule dynamics and alpha-tubulin acetylation, and TTR knockout results in increased dynamic microtubules and decreased regenerative capacity of axons.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Xinli Xu, Rui O. Beleza, Francisco Q. Goncalves, Sergio Valbuena, Sofia Alcada-Morais, Nelio Goncalves, Joana Magalhaes, Joao M. M. Rocha, Sofia Ferreira, Ana S. G. Figueira, Juan Lerma, Rodrigo A. Cunha, Ricardo J. Rodrigues, Joana M. Marques
Summary: This study reveals that adenosine A(2A) receptors (A(2A)R) contribute to circuit remodeling in the mature brain, specifically in the hippocampal mossy fiber (MF) sprouting found in diseases like temporal lobe epilepsy. A(2A)R activation in dentate granule cells induces the formation of abnormal secondary axons, which is activated by extracellular ATP-derived adenosine. These findings highlight the role of the CD73-A(2A)R axis in regulating circuit remodeling in the mature brain.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Filipa Gaspar-Silva, Diogo Trigo, Joana Magalhaes
Summary: Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. This review focuses on the molecular/cellular hallmarks associated with brain ageing, the impact of systemic ageing on brain ageing, and the rejuvenating strategies that have shown success in delaying brain ageing and related diseases.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Debora A. Moreira, Sofia D. Santos, Victoria Leiro, Ana P. Pego
Summary: Alzheimer's disease (AD) affects over 30 million people worldwide and is characterized by the accumulation of amyloid beta peptide and hyperphosphorylated tau aggregates in the brain. Currently, there are limited approved drugs for AD treatment, and the majority of patients have no disease-modifying options. Nanobiomaterials, especially dendrimers, offer potential as multifunctional and multitargeted therapies for AD. Dendrimers have unique characteristics as drug carriers and also display anti-amyloidogenic properties. This review discusses the properties of dendrimers and derivatives that make them excellent AD nanotherapeutics, their use as drugs, and the challenges in their clinical application.
Article
Materials Science, Biomaterials
Maria Lopes, Marilia Torrado, Daryl Barth, Sofia D. Santos, Melike Sever-Bahcekapili, Ayse B. Tekinay, Mustafa O. Guler, Franck Cleymand, Ana P. Pego, Joao Borges, Joao F. Mano
Summary: Peptide amphiphiles (PAs) are effective molecular building blocks for self-assembling nanobiomaterials. This study developed a simple approach to recreate the native neural extracellular matrix (ECM) using electrostatic-driven supramolecular presentation of a laminin-derived IKVAV-containing self-assembling PA (IKVAV-PA). The bioactive ECM-mimetic supramolecular nanofilms promote primary neuronal cells' adhesion, viability, morphology, and neurite outgrowth, making them promising for neural tissue regeneration.
BIOMATERIALS SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Raquel L. Pereira, Daniela Oliveira, Ana P. Pego, Sofia D. Santos, Felismina T. C. Moreira
Summary: This study reports a novel electrochemical miRNA biosensor for the diagnosis of Alzheimer's disease (AD). The biosensor, based on carbon screen-printed electrodes modified with gold nanostructures and a complementary anti-miR-34a oligonucleotide probe, showed good target affinity and selectivity. The biosensor displayed a wide linearity range and low detection limit, and it was not affected by serum compounds. Additionally, the biosensor successfully detected miR-34a in the cell culture medium. These findings suggest that the proposed biosensor could serve as a new, inexpensive, and minimally invasive tool for the early diagnosis of AD.
BIOELECTROCHEMISTRY
(2023)
