Progress in molecular biology and translational science最新文献

{"title":"Experimental techniques for detecting and evaluating the amyloid fibrils.","authors":"Farnoosh Farzam, Bahareh Dabirmanesh","doi":"10.1016/bs.pmbts.2024.03.004","DOIUrl":"10.1016/bs.pmbts.2024.03.004","url":null,"abstract":"<p><p>Amyloid fibrils are insoluble proteins with intricate β-sheet structures associated with various human diseases, including Parkinson's, Alzheimer's, and prion diseases. Proteins can form aggregates when their structure is misfolded, resulting in highly organized amyloid fibrils or amorphous aggregates. The formation of protein aggregates is a promising research field for mitigating diseases and the pharmaceutical and food industries. It is important to monitor and minimize the appearance of aggregates in these protein products. Several methods exist to assess protein aggregation, that includes from basic investigations to advanced biophysical techniques. Physicochemical parameters such as molecular weight, conformation, structure, and dimension are examined to study aggregation. There is an urgent need to develop methods for the detection of protein aggregation and amyloid fibril formation both in vitro and in vivo. This chapter focuses on a comprehensive discussion of the methods used to characterize and evaluate aggregates and amyloid fibrils.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"206 ","pages":"183-227"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liquid-liquid phase separation as triggering factor of fibril formation.","authors":"Fereshteh Ramezani Khorsand, Vladimir N Uversky","doi":"10.1016/bs.pmbts.2024.03.006","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.03.006","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) refers to the phenomenon, where a homogeneous solution spontaneously undergoes a transition into two or more immiscible phases. Through transient weak multivalent macromolecular interactions, a homogeneous solution can spontaneously separate into two phases: one rich in biomolecules and the other poor in biomolecules. Phase separation is believed to serve as the physicochemical foundation for the formation of membrane-less organelles (MLOs) and bio-molecular condensates within cells. Moreover, numerous biological processes depend on LLPS, such as transcription, immunological response, chromatin architecture, DNA damage response, stress granule formation, viral infection, etc. Abnormalities in phase separation can lead to diseases, such as cancer, neurodegeneration, and metabolic disorders. LLPS is regulated by various factors, such as concentration of molecules undergoing LLPS, salt concentration, pH, temperature, post-translational modifications, and molecular chaperones. Recent research on LLPS of biomolecules has progressed rapidly and led to the development of databases containing information pertaining to various aspects of the biomolecule separation analysis. However, more comprehensive research is still required to fully comprehend the specific molecular mechanisms and biological effects of LLPS.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"206 ","pages":"143-182"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current progress in CRISPR-Cas systems for autoimmune diseases.","authors":"Juveriya Israr, Ajay Kumar","doi":"10.1016/bs.pmbts.2024.07.011","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.07.011","url":null,"abstract":"<p><p>A body develops an autoimmune illness when its immune system mistakenly targets healthy cells and organs. Eight million people are affected by more than 80 autoimmune diseases. The public's and individuals' well-being is put at risk. Type 1 diabetes, lupus, rheumatoid arthritis, and multiple sclerosisare autoimmune diseases. Tissue injury, nociceptive responses, and persistent inflammation are the results of these stresses. Concerns about healthcare costs, health, and physical limitations contribute to these issues. Given their prevalence, it is crucial to enhance our knowledge, conduct thorough research, and provide all-encompassing support to women dealing with autoimmune diseases. This will lead to better public health and better patient outcomes. Most bacteria's immune systems employ CRISPR-Cas, a state-of-the-art technique for editing genes. For Cas to break DNA with pinpoint accuracy, a guide RNA employs a predetermined enzymatic pathway. Genetic modifications started. After it was developed, this method was subjected to much research on autoimmune diseases. By modifying immune pathways, CRISPR gene editing can alleviate symptoms, promote immune system tolerance, and decrease autoimmune reactivity. The autoimmune diseases that CRISPR-Cas9 targets now have no treatment or cure. Results from early clinical trials and preclinical studies of autoimmune medicines engineered using CRISPR showed promise. Modern treatments for rheumatoid arthritis,multiple sclerosis, and type 1 diabetes aim to alter specific genetic or immune mechanisms. Accurate CRISPR editing can fix autoimmune genetic disorders. Modifying effector cells with CRISPR can decrease autoimmune reactions. These cells include cytotoxic T and B lymphocytes. Because of improvements in delivery techniques and kits, CRISPR medications are now safer, more effective, and more accurately targeted. It all comes down to intricate immunological reactions and unexpected side consequences. Revolutionary cures for autoimmune problems and highly personalized medical therapies have been made possible by recent advancements in CRISPR.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"208 ","pages":"231-259"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and basic science aspects of innate lymphoid cells as novel immunotherapeutic targets in cancer treatment.","authors":"Eric Jou","doi":"10.1016/bs.pmbts.2024.03.036","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.03.036","url":null,"abstract":"<p><p>Immunotherapy has revolutionised cancer treatment over the past decade, demonstrating remarkable efficacy across a broad range of cancer types. However, not all patients or cancer types respond to contemporary clinically-utilised immunotherapeutic strategies, which largely focus on harnessing adaptive immune T cells for cancer treatment. Accordingly, it is increasingly recognised that upstream innate immune pathways, which govern and orchestrate the downstream adaptive immune response, may prove critical in overcoming cancer immunotherapeutic resistance. Innate lymphoid cells (ILCs) are the most recently discovered major innate immune cell population. They have overarching roles in homeostasis and orchestrating protective immunity against pathogens. As innate immune counterparts of adaptive immune T cells, ILCs exert effector functions through the secretion of cytokines and direct cell-to-cell contact, with broad influence on the overall immune response. Importantly, dysregulation of ILC subsets have been associated with a range of diseases, including immunodeficiency disorders, allergy, autoimmunity, and more recently, cancer. ILCs may either promote or inhibit cancer initiation and progression depending on the cancer type and the specific ILC subsets involved. Critically, therapeutic targeting of ILCs and their associated cytokines shows promise against a wide range of cancer types in both preclinical models and early phase oncology clinical trials. This chapter provides a comprehensive overview of the current understanding of ILC subsets and the associated cytokines they produce in cancer pathogenesis, with specific focus on how these innate pathways are, or can be targeted, therapeutically to overcome therapeutic resistance and ultimately improve patient care.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"209 ","pages":"1-60"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in the polymeric nanoparticulate delivery systems for RNA therapeutics.","authors":"Sristi, Waleed H Almalki, Ritu Karwasra, Garima Gupta, Surender Singh, Ajay Sharma, Amirhossein Sahebkar, Prashant Kesharwani","doi":"10.1016/bs.pmbts.2024.01.001","DOIUrl":"10.1016/bs.pmbts.2024.01.001","url":null,"abstract":"<p><p>RNA therapeutics have emerged as potential treatments for genetic disorders, infectious diseases, and cancer. RNA delivery to target cells for efficient therapeutic applications remains challenging due to instability and poor uptake. Polymeric nanoparticulate delivery systems offer stability, protection, and controlled release. These systems shield RNA from degradation, enabling efficient uptake and extended circulation. Various polymeric nanoparticle platforms have been explored, including lipid-based nanoparticles, polymeric micelles, dendrimers, and polymer-drug conjugates. This review outlines recent breakthroughs of recent advances, design principles, characterization techniques, and performance evaluation of these delivery systems. It highlights their potential in translating preclinical studies into clinical applications. Additionally, the review discusses the application of polymeric nanoparticles in ophthalmic drug delivery, particularly for medications that dissolve poorly in water, and the progress made in siRNA-based therapies for viral infections, autoimmune diseases, and cancers. SiRNA holds great promise for precision medicine and therapeutic intervention, with the ability to target specific genes and modulate disease-associated pathways. The versatility and potency of siRNA-based drugs offer a broader scope for therapeutic intervention compared to traditional biological drugs. As research in RNA therapeutics continues to advance, these technologies hold tremendous potential to revolutionize the treatment of various diseases and improve patient outcomes.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"204 ","pages":"219-248"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140065804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathways of amyloid fibril formation and protein aggregation.","authors":"Elaheh Tavili, Fatemeh Aziziyan, Bahareh Dabirmanesh","doi":"10.1016/bs.pmbts.2024.03.010","DOIUrl":"10.1016/bs.pmbts.2024.03.010","url":null,"abstract":"<p><p>The main cause of many neurodegenerative diseases and systemic amyloidoses is protein and peptide aggregation and the formation of amyloid fibrils. The study of aggregation mechanisms, the discovery and description of aggregate structures, and a comprehensive understanding of the molecular mechanisms of amyloid formation are of great importance for the diagnostic processes at the molecular level and for the development of therapeutic strategies to counter aggregation-associated disorders. Given that understanding protein misfolding phenomena is directly related to the protein folding process, we will briefly explain the protein folding mechanism and then discuss the important factors involved in protein aggregation. In the following, we review different mechanisms of amyloid formation and finally represent the current knowledge on how amyloid fibrils are formed based on kinetic and thermodynamic factors.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"206 ","pages":"11-54"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein aggregation: An overview.","authors":"Bahareh Dabirmanesh, Khosro Khajeh, Vladimir N Uversky","doi":"10.1016/bs.pmbts.2024.03.007","DOIUrl":"10.1016/bs.pmbts.2024.03.007","url":null,"abstract":"<p><p>In order for an ordered protein to perform its specific function, it must have a specific molecular structure. Information about this structure is encoded in the protein's amino acid sequence. The unique functional state is achieved as a result of a specific process, known as protein folding. However, as a result of partial or complete unfolding of the polypeptide chain, proteins may misfold and aggregate, leading to the formation of various aggregated structures, such as like amyloid aggregates with the cross-β structure. A variety of cellular biological processes can be affected by protein aggregates that consume essential factors necessary for maintaining proteostasis, which leads to the proteostasis imbalance and further accumulation of protein aggregates, often resulting in age-related neurodegenerative disease progression and aging. However, in addition to their well-established pathological effects, amyloids also play various physiological roles, and many important biological processes involve such 'functional amyloids'. This chapter represents a brief overview of the protein aggregation phenomenon outlines a timeline provides of some key discoveries in this exciting field.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"206 ","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug repurposing for rare diseases.","authors":"Juveriya Israr, Shabroz Alam, Ajay Kumar","doi":"10.1016/bs.pmbts.2024.03.034","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.03.034","url":null,"abstract":"<p><p>Repurposing drugs for rare diseases is a creative and cost-efficient method for creating new treatment options for certain conditions. This technique entails repurposing existing pharmaceuticals for new uses by utilizing established information regarding pharmacological characteristics, modes of operation, safety profiles, and interactions with biological systems. Creating new treatments for uncommon diseases is frequently difficult because of factors including small patient groups, disease intricacy, and insufficient knowledge of disease pathobiology. Drug repurposing is a more efficient and cost-effective approach compared to developing new drugs from scratch. It typically requires collaboration among academia, pharmaceutical firms, and patient advocacy groups.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"207 ","pages":"231-247"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preface.","authors":"","doi":"10.1016/S1877-1173(24)00207-2","DOIUrl":"https://doi.org/10.1016/S1877-1173(24)00207-2","url":null,"abstract":"","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"209 ","pages":"xiii-xv"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The promise, progress, and challenges of in situ immunization agents in cancer immunotherapy.","authors":"Matthew J Giacalone","doi":"10.1016/bs.pmbts.2024.02.004","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.02.004","url":null,"abstract":"<p><p>In situ immunization (ISI) agents are an emerging and diverse class of locally acting cancer immunotherapeutic agents designed to promote innate immune activation in the early steps of the cancer immunity cycle to ultimately support development of a systemic tumor-specific immune response and protective immunologic memory. The aims of this review are to: (i) provide an introduction to ISI; (ii) summarize the history of ISI agents; (iii) expound upon the mechanism(s) and therapeutic objective(s) of ISI; (iv) compare the various approaches and therapeutic modalities developed and investigated to date; and (v) summarize clinical experiences in an effort to highlight the utility as well as the lessons and challenges of this promising approach. A prospective roadmap for future clinical development is provided that focuses on early and late-stage trial design considerations, the rationale and importance of investigating combination treatment, and the prospective use of ISI agents in the neoadjuvant setting.</p>","PeriodicalId":21157,"journal":{"name":"Progress in molecular biology and translational science","volume":"209 ","pages":"127-164"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}