Progress in molecular biology and translational science最新文献

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.

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.

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.

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.

Neurodegenerative diseases (NDDs) are neuronal problems that include the brain and spinal cord and result in loss of sensory and motor dysfunction. Common NDDs include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Multiple Sclerosis (MS), and Amyotrophic Lateral Sclerosis (ALS) etc. The occurrence of these diseases increases with age and is one of the challenging problems among elderly people. Though, several scientific research has demonstrated the key pathologies associated with NDDs still the underlying mechanisms and molecular details are not well understood and need to be explored and this poses a lack of effective treatments for NDDs. Several lines of evidence have shown that NDDs have a high prevalence and affect more than a billion individuals globally but still, researchers need to work forward in identifying the best therapeutic target for NDDs. Thus, several researchers are working in the directions to find potential therapeutic targets to alter the disease pathology and treat the diseases. Several steps have been taken to identify the early detection of the disease and drug repurposing for effective treatment of NDDs. Moreover, it is logical that current medications are being evaluated for their efficacy in treating such disorders; therefore, drug repurposing would be an efficient, safe, and cost-effective way in finding out better medication. In the current manuscript we discussed the utilization of drugs that have been repurposed for the treatment of AD, PD, HD, MS, and ALS.

In the dynamic landscape of cancer therapeutics, the innovative strategy of drug repurposing emerges as a transformative paradigm, heralding a new era in the fight against malignancies. This book chapter aims to embark on the comprehension of the strategic deployment of approved drugs for repurposing and the meticulous journey of drug repurposing from earlier times to the current era. Moreover, the chapter underscores the multifaceted and complex nature of cancer biology, and the evolving field of cancer drug therapeutics while emphasizing the mandate of drug repurposing to advance cancer therapeutics. Importantly, the narrative explores the latest tools, technologies, and cutting-edge methodologies including high-throughput screening, omics technologies, and artificial intelligence-driven approaches, for shaping and accelerating the pace of drug repurposing to uncover novel cancer therapeutic avenues. The chapter critically assesses the breakthroughs, expanding the repertoire of repurposing drug candidates in cancer, and their major categories. Another focal point of this book chapter is that it addresses the emergence of combination therapies involving repurposed drugs, reflecting a shift towards personalized and synergistic treatment approaches. The expert analysis delves into the intricacies of combinatorial regimens, elucidating their potential to target heterogeneous cancer populations and overcome resistance mechanisms, thereby enhancing treatment efficacy. Therefore, this chapter provides in-depth insights into the potential of repurposing towards bringing the much-needed big leap in the field of cancer therapeutics.

Protozoan parasites are major hazards to human health, society, and the economy, especially in equatorial regions of the globe. Parasitic diseases, including leishmaniasis, malaria, and others, contribute towards majority of morbidity and mortality. Around 1.1 million people die from these diseases annually. The lack of licensed vaccinations worsens the worldwide impact of these diseases, highlighting the importance of safe and effective medications for their prevention and treatment. However, the appearance of drug resistance in parasites continuously affects the availability of medications. The demand for novel drugs motivates global antiparasitic drug discovery research, necessitating the implementation of many innovative ways to maintain a continuous supply of promising molecules. Drug repurposing has come out as a compelling tool for drug development, offering a cost-effective and efficient alternative to standard de novo approaches. A thorough examination of drug repositioning candidates revealed that certain drugs may not benefit significantly from their original indications. Still, they may exhibit more pronounced effects in other disorders. Furthermore, certain medications can produce a synergistic effect, resulting in enhanced therapeutic effectiveness when given together. In this chapter, we outline the approaches employed in drug repurposing (sometimes referred to as drug repositioning), propose novel strategies to overcome these hurdles and fully exploit the promise of drug repurposing. We highlight a few major human protozoan diseases and a range of exemplary drugs repurposed for various protozoan infections, providing excellent outcomes for each disease.

β-thalassemia is an autosomal recessive disease, caused by one or more mutations in the β-globin gene that reduces or abolishes β-globin chain synthesis causing an imbalance in the ratio of α- and β-globin chain. Therefore, the ability to target mutations will provide a good result in the treatment of β-thalassemia. RNA therapeutics represents a promising class of drugs inclusive antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and APTAMER have investigated in clinical trials for treatment of human diseases as β-thalassemia; Especially, ASO therapeutics can completely treat β-thalassemia patients by the way of making ASO infiltrating through erythrocyte progenitor cells, migrating to the nucleus and hybridizing with abnormal splicing sites to suppress an abnormal splicing pattern of β-globin pre-mRNA. As a result, the exactly splicing process is restored to increase the expression of β-globin which increases the amount of mature hemoglobin of red blood cells of β-thalassemia patients. Furthermore, current study demonstrates that RNA-based therapeutics get lots of good results for β-thalassemia patients. Then, this chapter focuses on current advances of RNA-based therapeutics and addresses current challenges with their development and application for treatment of β-thalassemia patients.

Cell and gene therapy are innovative biomedical strategies aimed at addressing diseases at their genetic origins. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) systems have become a groundbreaking tool in cell and gene therapy, offering unprecedented precision and versatility in genome editing. This chapter explores the role of CRISPR in gene editing, tracing its historical development and discussing biomolecular formats such as plasmid, RNA, and protein-based approaches. Next, we discuss CRISPR delivery methods, including viral and non-viral vectors, followed by examining the various engineered CRISPR variants for their potential in gene therapy. Finally, we outline emerging clinical applications, highlighting the advancements in CRISPR for breakthrough medical treatments.