Progress in Molecular Biology and Translational Science最新文献_第2页

Recent progress in CRISPR/Cas9 system for eye disorders. CRISPR/Cas9系统治疗眼部疾病的最新进展。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-08-17 DOI: 10.1016/bs.pmbts.2024.07.018

D A Ayush Gowda, Girish Birappa, Sripriya Rajkumar, C Bindu Ajaykumar, Bhavana Srikanth, Sammy L Kim, Vijai Singh, Aparna Jayachandran, Junwon Lee, Suresh Ramakrishna

{"title":"Recent progress in CRISPR/Cas9 system for eye disorders.","authors":"D A Ayush Gowda, Girish Birappa, Sripriya Rajkumar, C Bindu Ajaykumar, Bhavana Srikanth, Sammy L Kim, Vijai Singh, Aparna Jayachandran, Junwon Lee, Suresh Ramakrishna","doi":"10.1016/bs.pmbts.2024.07.018","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.07.018","url":null,"abstract":"Ocular disorders encompass a broad spectrum of phenotypic and clinical symptoms resulting from several genetic variants and environmental factors. The unique anatomy and physiology of the eye facilitate validation of cutting-edge gene editing treatments. Genome editing developments have allowed researchers to treat a variety of diseases, including ocular disorders. The clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) system holds considerable promise for therapeutic applications in the field of ophthalmology, including repair of aberrant genes and treatment of retinal illnesses related to the genome or epigenome. Application of CRISPR/Cas9 systems to the study of ocular disease and visual sciences have yielded innovations including correction of harmful mutations in patient-derived cells and gene modifications in several mammalian models of eye development and disease. In this study, we discuss the generation of several ocular disease models in mammalian cell lines and in vivo systems using a CRISPR/Cas9 system. We also provide an overview of current uses of CRISPR/Cas9 technologies for the treatment of ocular pathologies, as well as future challenges.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"210 ","pages":"21-46"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014988","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}

引用次数: 0

Preface.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 DOI: 10.1016/S1877-1173(25)00027-4

Tanveer A Dar, Laishram R Singh, Vladimir N Uversky

引用次数: 0

Preface. 前言。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 DOI: 10.1016/S1877-1173(25)00011-0

Vijai Singh

引用次数: 0

Molecular crowding and amyloidogenic self-assembly: Emergent perspectives from modern computations.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2025-01-21 DOI: 10.1016/bs.pmbts.2024.10.001

Hindol Chatterjee, Neelanjana Sengupta

{"title":"Molecular crowding and amyloidogenic self-assembly: Emergent perspectives from modern computations.","authors":"Hindol Chatterjee, Neelanjana Sengupta","doi":"10.1016/bs.pmbts.2024.10.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.10.001","url":null,"abstract":"In recent decades, the conventional protein folding paradigm has been challenged by intriguing properties of disordered peptide sequences that do not adopt stably folded conformations. Such intrinsically disordered proteins and protein regions (IDPs and IDRs) are poised uniquely in biology due to their propensity for self-aggregation, amyloidogenesis, and correlations with a cluster of debilitating diseases. Complexities underlying their structural and functional manifestations are enhanced in the presence of molecular crowding via non-specific protein-protein and protein-solvent contacts. Enabled by technological advances, physics-based algorithms, and data science, modern computer simulations provide unprecedented insights into the structure, function, dynamics, and thermodynamics of complex macromolecular systems. These characteristics are frequently correlated and manifest into unique observables. This chapter presents an overview of how such methodologies can lend insights and drive investigations into the molecular trifecta of crowding, protein self-aggregation, and amyloidogenesis. It begins with a general overview of disordered proteins in relation to biological function and of a suite of relevant experimental methods. Specific examples are showcased in the biological context. This is followed by a description of the computational approaches that supplant experimental efforts, with an elaboration on enhanced molecular simulation methods. The chapter concludes by alluding to expanded possibilities in disease amelioration.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"209-247"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415887","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}

引用次数: 0

Strategies for inhibiting amyloid fibrillation: Current status and future prospects.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2025-01-21 DOI: 10.1016/bs.pmbts.2024.09.001

Md Nadir Hassan, Murtaza Hussain, Rizwan Hasan Khan

引用次数: 0

The Huntington's disease drug pipeline: a review of small molecules and their therapeutic targets.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-10-16 DOI: 10.1016/bs.pmbts.2024.08.006

Sameera Khan, Nargis Bano, Vladimir N Uversky, Shakir Ahamad, Shahnawaz Ali Bhat

{"title":"The Huntington's disease drug pipeline: a review of small molecules and their therapeutic targets.","authors":"Sameera Khan, Nargis Bano, Vladimir N Uversky, Shakir Ahamad, Shahnawaz Ali Bhat","doi":"10.1016/bs.pmbts.2024.08.006","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.08.006","url":null,"abstract":"Huntington's disease (HD) is a progressive neurodegenerative condition resulting from a CAG repeat expansion in the huntingtin gene (HTT). Recent advancements in understanding HD's cellular and molecular pathways have paved the way for identifying various effective small-molecule candidates to treat the disorder. Two small molecules, Tetrabenazine and Deutetrabenazine, are approved for managing chorea associated with HD, and several others are under clinical trials. Notably, the field of small-molecule therapeutics targeting HD is rapidly progressing, and there is anticipation of their approval in the foreseeable future. This chapter provides a comprehensive overview of the emergence of small-molecule therapeutics in various stages of clinical development for HD therapy. The emphasis is placed on detailing their structural design, therapeutic effects, and specific mechanisms of action. Additionally, exploring key drivers implicated in HD pathogenesis offers valuable insights, as a foundational principle for designing prospective anti-HD therapeutic leads.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"169-207"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415908","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}

引用次数: 0

Factors responsible for alpha-Synuclein aggregation.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2025-01-25 DOI: 10.1016/bs.pmbts.2024.11.004

Khuraijam Surjalal Singh, Rahul Verma, Nagendra Singh, Laishram Rajendrakumar Singh, Akshita Gupta

{"title":"Factors responsible for alpha-Synuclein aggregation.","authors":"Khuraijam Surjalal Singh, Rahul Verma, Nagendra Singh, Laishram Rajendrakumar Singh, Akshita Gupta","doi":"10.1016/bs.pmbts.2024.11.004","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.11.004","url":null,"abstract":"Aggregation of α-Synuclein (α-Syn) is the hallmark of the pathophysiology of Parkinson's disease. Apart from aggregates, α-Syn can exist in multiple abnormal forms such as oligomers, protofibrils, fibrils amorphous aggregates etc. These forms initiate aggressive, selective and progressive neuronal atrophy through various modes such as mitochondrial dysfunction, lysosomal malfunction, and disruption of calcium homeostasis in various α-Syn-related neurodegenerative disorders. Structurally α-Syn is divided into three domains: N-terminal region made by amino acids1-67 (amphipathic, lysine-rich and interacts with acidic lipid membranes), Non-amyloid-β component (NAC) region made by amino acids 67-95 (hydrophobic region, central to α-syn aggregation) and C-terminal region made by amino acids 96-140 (acidic and proline-rich region responsible for interaction with other proteins). α-Syn follows the pattern of a typical intrinsically disordered protein and lacks a proper folded conformation and exist majorly in a random coil form, though on lipid binding the protein assumes an α-helical structure. The central random coil region of α-Syn is involved in fibril formation transforming into β-sheet rich secondary structures which is a characteristic of amyloids. This chapter entails an elaborate explanation of factors influencing the structure, function and aggregation of α-Syn. Major factors being abnormally high physiological expression of the protein, mutations, posttranslational modifications and also interactions with small molecules such as osmolytes in the cellular milieu. Studying the factors responsible for misfolding and aggregation of α-Syn along with the mechanism involved is crucial to understanding their implications in Parkinson's disease, and will yield valuable insights into disease mechanisms, potential therapeutic strategies.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"271-292"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415501","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}

引用次数: 0

Effect of osmolytes and posttranslational modifications on modulating the chaperone function of α-crystallin.

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-10-11 DOI: 10.1016/bs.pmbts.2024.09.002

Khuraijam Surjalal Singh, Snigdha Krishna, Akshita Gupta, Laishram Rajendrakumar Singh

{"title":"Effect of osmolytes and posttranslational modifications on modulating the chaperone function of α-crystallin.","authors":"Khuraijam Surjalal Singh, Snigdha Krishna, Akshita Gupta, Laishram Rajendrakumar Singh","doi":"10.1016/bs.pmbts.2024.09.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.09.002","url":null,"abstract":"Proteins are responsible for a vast majority of various cellular effector processes. α-crystallin is one of the most important proteins in the lens of the eye, which acts as a molecular chaperone that keeps the lens transparent and refractive. α-crystallin is categorized as an intrinsically disordered protein (IDP), devoid of a stable three-dimensional structure, in contrast to conventional globular proteins. Because of its structural flexibility, it can stop denatured proteins from aggregating and building up within the lens over time. α-crystallin's dynamic quaternary structure, which allows it to exist in a variety of oligomeric forms, from dimers to massive assemblies, improves its chaperone function and flexibility. Its intrinsically disordered nature enables it to interact with a variety of client proteins due to its large non-polar and polar residue content and lack of a hydrophobic core. Furthermore, under physiological stress, osmolytes like sorbitol, TMAO, and urea are essential in regulating the stability and function of α-crystallin. Post-translational modifications (PTMs) such as glycation, in which reducing sugars combine with amino groups on the protein to generate advanced glycation end-products, impair α-crystallin's ability to function. These AGEs can cross-link α-crystallin molecules to prevent protein aggregation, changing their structure and decreasing their chaperone action. Because of their raised blood glucose levels, diabetics have an increased chance of developing cataracts as a result of this process. Comprehending how glycation and other PTMs affect α-crystallin is crucial for formulating treatment plans to maintain lens transparency and fight cataracts linked to aging and metabolic disorders.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"211 ","pages":"89-111"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415500","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}

引用次数: 0

CRISPR challenges in clinical developments. CRISPR在临床发展中的挑战。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-08-15 DOI: 10.1016/bs.pmbts.2024.08.001

Mohadeseh Khoshandam, Hossein Soltaninejad, Iman Bhia, Mohammad Taghi Hedayati Goudarzi, Saman Hosseinkhani

引用次数: 0

Current approaches in CRISPR-Cas systems for diabetes. 目前治疗糖尿病的CRISPR-Cas系统的方法。

3区生物学

Progress in Molecular Biology and Translational Science Pub Date : 2025-01-01 Epub Date: 2024-08-30 DOI: 10.1016/bs.pmbts.2024.08.002

Vishnu Kirthi Arivarasan, Diksha Diwakar, Neethu Kamarudheen, Karthik Loganathan

{"title":"Current approaches in CRISPR-Cas systems for diabetes.","authors":"Vishnu Kirthi Arivarasan, Diksha Diwakar, Neethu Kamarudheen, Karthik Loganathan","doi":"10.1016/bs.pmbts.2024.08.002","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2024.08.002","url":null,"abstract":"In the face of advancements in health care and a shift towards healthy lifestyle, diabetes mellitus (DM) still presents as a global health challenge. This chapter explores recent advancements in the areas of genetic and molecular underpinnings of DM, addressing the revolutionary potential of CRISPR-based genome editing technologies. We delve into the multifaceted relationship between genes and molecular pathways contributing to both type1 and type 2 diabetes. We highlight the importance of how improved genetic screening and the identification of susceptibility genes are aiding in early diagnosis and risk stratification. The spotlight then shifts to CRISPR-Cas9, a robust genome editing tool capable of various applications including correcting mutations in type 1 diabetes, enhancing insulin production in T2D, modulating genes associated with metabolism of glucose and insulin sensitivity. Delivery methods for CRISPR to targeted tissues and cells are explored, including viral and non-viral vectors, alongside the exciting possibilities offered by nanocarriers. We conclude by discussing the challenges and ethical considerations surrounding CRISPR-based therapies for DM. These include potential off-target effects, ensuring long-term efficacy and safety, and navigating the ethical implications of human genome modification. This chapter offers a comprehensive perspective on how genetic and molecular insights, coupled with the transformative power of CRISPR, are paving the way for potential cures and novel therapeutic approaches for DM.","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"210 ","pages":"95-125"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143014967","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}

引用次数: 0