Advances in protein chemistry and structural biology最新文献_第2页

Therapeutic insight into the role of nuclear protein HNF4α in liver carcinogenesis. 核蛋白HNF4α在肝癌发生中的治疗作用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-06-15 DOI: 10.1016/bs.apcsb.2024.05.001

Soumik Das, Harini Ravi, V Devi Rajeswari, Ganesh Venkatraman, Magesh Ramasamy, Sivaraman Dhanasekaran, Gnanasambandan Ramanathan

{"title":"Therapeutic insight into the role of nuclear protein HNF4α in liver carcinogenesis.","authors":"Soumik Das, Harini Ravi, V Devi Rajeswari, Ganesh Venkatraman, Magesh Ramasamy, Sivaraman Dhanasekaran, Gnanasambandan Ramanathan","doi":"10.1016/bs.apcsb.2024.05.001","DOIUrl":"10.1016/bs.apcsb.2024.05.001","url":null,"abstract":"Hepatocyte nuclear factor 4-alpha (HNF4α), a well-preserved member of the nuclear receptor superfamily of transcription factors, is found in the liver. It is recognized as a central controller of gene expression specific to the liver and plays a key role in preserving the liver's homeostasis. Irregular expression of HNF4α is increasingly recognized as a crucial factor in the proliferation, cell death, invasiveness, loss of specialized functions, and metastasis of cancer cells. An increasing number of studies are pointing to abnormal HNF4α expression as a key component of cancer cell invasion, apoptosis, proliferation, dedifferentiation, and metastasis. Understanding HNF4α's intricate involvement in liver carcinogenesis provides a promising avenue for therapeutic intervention. This chapter attempts to shed light on the diverse aspects of HNF4's role in liver carcinogenesis and demonstrate how this knowledge can be harnessed for approaches to prevent and treat liver cancer. This comprehensive chapter will offer an elaborate perspective on HNF4's function in liver cancer, delineating its molecular mechanisms that aid in the emergence of liver cancer. Furthermore, it will highlight the potential to help create more effective and precisely targeted therapeutic strategies, rekindling fresh optimism in the fight against this formidable condition.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"1-37"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021814","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

Small molecule-mediated therapeutic approaches to target Tau and Alzheimer's disease. 靶向Tau蛋白和阿尔茨海默病的小分子介导治疗方法。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-12-05 DOI: 10.1016/bs.apcsb.2024.11.010

Subashchandrabose Chinnathambi

{"title":"Small molecule-mediated therapeutic approaches to target Tau and Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2024.11.010","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.010","url":null,"abstract":"Neurodegeneration is marked by the altered proteostasis and protein degradation mechanism. This is caused due to the accumulation of aberrant proteins. Alzheimer's disease is one of the leading causes of neurodegeneration characterized by the aggregation of Tau and Amyloid-β proteins intracellularly and extracellularly, respectively. The intracellular aggregation of Tau triggers accumulation of oxidative stress, loss of ER and mitochondrial function, leading to the aggravation of aggregates formation. Thus, increasing the load of aberrant proteins on chaperones and degradative mechanism, such as autophagy and ubiquitin-proteasome system. Although several small molecules are known to target and prevent Tau aggregation, the detrimental effects in the cell due to aggregates accumulation shall not be overlooked. In such instance, small molecules that effectively target Tau aggregates and the cellular aberrations would be of great importance. Here we have discussed the efficacy of natural molecule, Limonoid, isolated from Azadirachta indica that prevents Tau aggregation and also activates the heat shock protein system. The activated heat shock protein system elevates the levels of Hsp70 that is known to interact with aberrantly folded Tau. Further, the role of Hsp70 in directing Tau clearance by macroautophagy or chaperone-mediated autophagy elucidates the effect of limonoids in overcoming AD pathology due to Tau aggregation.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"287-304"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955735","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

Exploring therapeutic strategies based on chaperon-mediated disaggregation. 探索基于伴侣介导的解聚的治疗策略。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-03-31 DOI: 10.1016/bs.apcsb.2024.11.003

Leandro Rocha Silva, Sheila Oliveira de Souza, Ana Catarina Rezende Leite, Edeildo Ferreira da Silva-Júnior

{"title":"Exploring therapeutic strategies based on chaperon-mediated disaggregation.","authors":"Leandro Rocha Silva, Sheila Oliveira de Souza, Ana Catarina Rezende Leite, Edeildo Ferreira da Silva-Júnior","doi":"10.1016/bs.apcsb.2024.11.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.003","url":null,"abstract":"In the quest to develop effective therapeutic strategies for diseases associated with protein misfolding and aggregation, molecular chaperones have emerged as pivotal players. This chapter explores the role of chaperones, such as Hsp40, Hsp70, and Hsp90, in mediating the disaggregation of misfolded proteins and facilitating proper folding under stress conditions. Despite their lack of sequence specificity, these proteins adeptly recognize exposed hydrophobic regions in partially folded states, thereby preventing aggregation and promoting functional conformations. The intricate network of chaperone interactions is crucial for maintaining cellular homeostasis and mitigating the pathological consequences of protein misfolding, particularly in conditions like Alzheimer's disease and various cancers. Innovative therapeutic approaches, including the use of pharmacological and chemical chaperones, aim to restore functionality to mutated or misfolded proteins, exemplified by interventions targeting the ΔF508 mutation in CFTR. While promising, the modulation of chaperone activity must be carefully calibrated to avoid disrupting cellular functions. This chapter highlights the potential of chaperone-mediated disaggregation as a therapeutic strategy, addressing both the current advancements and the challenges that lie ahead in harnessing these proteins for clinical benefit.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"219-254"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961775","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

Heat shock proteins regulates Tau protein aggregation in Alzheimer's disease. 热休克蛋白调节阿尔茨海默病中Tau蛋白的聚集。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-09-11 DOI: 10.1016/bs.apcsb.2024.08.003

Subashchandrabose Chinnathambi

{"title":"Heat shock proteins regulates Tau protein aggregation in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi","doi":"10.1016/bs.apcsb.2024.08.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.08.003","url":null,"abstract":"Alzheimer's disease is one of the neurodegenerative diseases characterized by loss of integrity and function of the cell, leading to progressive neuronal loss and ultimately dementia. Tau is one of the most soluble protein mainly involved in assembly and disassembly of microtubules (MT) which helps in the anterograde and retrograde transport of cargos. However in AD conditions Tau is subjected to various insults such as hyperphosphorylation, glycation, glycosylation, truncation, acetylation, oxidation etc., which leads to the loss-of-function. Thus modified Tau loses its affinity for MT and aggregates to form toxic oligomers followed by matured neurofibrillary tangles (NFTs) which attains cross-β structure. The cellular machinery such as chaperones, ubiquitin-proteasome system (UPS) and lysosomes tries to resolve these aggregates and helps in its clearance. During AD pathology the cellular machinery fails to clear aggregates and leads to neuronal death. In this aspect several strategies have been employed to prevent Tau aggregation that includes inhibitors for kinases, activators for phosphatases, small molecule activators of heat shock protein response and small molecules that can prevent Tau aggregation and increases its association with chaperones.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"146 ","pages":"161-178"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558788","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

Tau protein aggregation: A therapeutic target for neurodegenerative diseases. Tau蛋白聚集：神经退行性疾病的治疗靶点。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-05-12 DOI: 10.1016/bs.apcsb.2024.11.012

Aryan Duggal, Drishti Mahindru, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati

{"title":"Tau protein aggregation: A therapeutic target for neurodegenerative diseases.","authors":"Aryan Duggal, Drishti Mahindru, Kirti Baghel, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.11.012","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.11.012","url":null,"abstract":"Tau protein, a critical element for neuronal structure, becomes pathogenic in numerous neurodegenerative diseases, particularly Alzheimer's disease and other tauopathies. Under normal conditions, tau stabilizes microtubules and supports essential cellular transport systems. However, in disease states, tau undergoes abnormal modifications-most notably hyperphosphorylation-causing it to detach from microtubules and aggregate into neurofibrillary tangles. These aggregates disrupt neuronal function, leading to progressive cognitive and motor deficits. This chapter provides a comprehensive overview of tau's structural properties, normal cellular roles, and the cascade of pathological changes that transform it into a neurotoxic agent. We examine current therapeutic strategies targeting tau, including efforts to inhibit its phosphorylation, prevent aggregation, and enhance its clearance from cells. Approaches such as kinase inhibitors, immunotherapies, and gene-based therapies are discussed in the context of their potential to halt or slow disease progression. Additionally, recent advancements in diagnostic tools-such as tau-specific PET imaging and blood biomarkers-are highlighted as transformative for early detection of the disease .","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"146 ","pages":"77-136"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558792","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

The aggregation propensity of Tau and amyloid-β in Alzheimer's disease. 阿尔茨海默病中Tau和淀粉样蛋白-β的聚集倾向。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-04-02 DOI: 10.1016/bs.apcsb.2024.10.004

Subashchandrabose Chinnathambi, Murugappan Kumarappan, Madhura Chandrashekar, Sneha Malik

引用次数: 0

Preface. 前言。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 DOI: 10.1016/S1876-1623(25)00019-7

Dr Vijay Kumar Prajapati

引用次数: 0

Nuclear Tau accumulation in Alzheimer's disease. 阿尔茨海默病的核Tau积聚。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-06-21 DOI: 10.1016/bs.apcsb.2024.06.003

Subashchandrabose Chinnathambi, Gowshika Velmurugan, Swathi Suresh, Anusree Adithyan, Madhura Chandrashekar

{"title":"Nuclear Tau accumulation in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Gowshika Velmurugan, Swathi Suresh, Anusree Adithyan, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2024.06.003","DOIUrl":"10.1016/bs.apcsb.2024.06.003","url":null,"abstract":"Tau is a well-known microtubule-associated protein and is located in the cytoplasm of neurons, which play a crucial role in Alzheimer's diseases. Due to its preferred binding to DNA sequences found in the nucleolus and pericentromeric heterochromatin, Tau has been found within the cell nucleus, where it may be a nucleic acid-associated protein. Tau has the ability to directly interact with nuclear pore complex nucleoporins, influencing both their structural and functional integrity. The interaction between Tau and NUPs highlights a potential mechanism underlying NPC dysfunction in AD pathogenesis. Pathological Tau hinders the import and export of nucleus through RAN mediated cascades. Nuclear Tau aggregates colocalize with membrane less organelles called nuclear speckles, which are involved in pre-mRNA splicing, and modify their dynamics, composition, and structure. Additionally, SRRM2 and other nuclear speckle proteins including MSUT2 and PABPN1 mislocalize to cytosolic Tau aggregates, and causes propagation of Tau aggregates. Research highlights, Extracellular Tau Oligomers induce significant nuclear invagination. They act as a key player in the transformation of healthy neurons into sick neurons in AD. The mechanism behind this phenomenon depends on intracellular Tau and is linked to changes in chromatin structure, nucleocytoplasmic transport, and gene transcription. This review highlights the vital roles of nuclear Tau protein in the context of nuclear pore complex functioning and, modulation of nuclear speckles in Alzheimer's diseases. Addressing these pathways is essential for formulating focused therapeutics intended to alleviate Tau-induced neurodegeneration.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"143 ","pages":"323-337"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021799","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

Exploring immunotherapy to control human infectious diseases. 探索免疫疗法控制人类传染病。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-12-22 DOI: 10.1016/bs.apcsb.2024.10.010

Praveen Rai, Sanjana Mehrotra, Vijay Kumar Prajapati

{"title":"Exploring immunotherapy to control human infectious diseases.","authors":"Praveen Rai, Sanjana Mehrotra, Vijay Kumar Prajapati","doi":"10.1016/bs.apcsb.2024.10.010","DOIUrl":"10.1016/bs.apcsb.2024.10.010","url":null,"abstract":"Infectious diseases continue to pose significant challenges to global health, especially with the rise of antibiotic resistance and emerging pathogens. Traditional treatments, while effective, are often limited in the face of rapidly evolving pathogens. Immunotherapy, which harnesses and enhances the body's immune response, offers a promising alternative to conventional approaches for the treatment of infectious diseases. By employing use of monoclonal antibodies, vaccines, cytokine therapies, and immune checkpoint inhibitors, immunotherapy has demonstrated considerable potential in overcoming treatment resistance and improving patient outcomes. Key innovations, including the development of mRNA vaccines, use of immune modulators, adoptive cell transfer, and chimeric antigen receptor (CAR)-T cell therapy are paving the way for more targeted pathogen clearance. Further, combining immunotherapy with conventional antibiotic treatment has demonstrated effectiveness against drug-resistant strains, but this chapter explores the evolving field of immunotherapy for the treatment of bacterial, viral, fungal, and parasitic infections. The chapter also explores the recent breakthroughs and ongoing clinical trials in infectious disease immunotherapy.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"389-429"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466726","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

Role of protein aggregates in bacteria. 蛋白质聚集体在细菌中的作用。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2024-10-10 DOI: 10.1016/bs.apcsb.2024.09.012

Ewa Laskowska, Dorota Kuczyńska-Wiśnik, Karolina Stojowska-Swędrzyńska

{"title":"Role of protein aggregates in bacteria.","authors":"Ewa Laskowska, Dorota Kuczyńska-Wiśnik, Karolina Stojowska-Swędrzyńska","doi":"10.1016/bs.apcsb.2024.09.012","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2024.09.012","url":null,"abstract":"Protein misfolding and aggregation in bacteria, induced by a variety of intrinsic and environmental stresses, have often been associated with proteostasis disruption and toxic effects. However, a growing body of evidence suggests that these aggregates may also serve as functional membrane-less organelles (MLOs), playing a protective role in bacterial cells. The main mechanism responsible for the formation of MLOs is liquid-liquid phase separation (LLPS), a process that transforms a homogenous solution of macromolecules into dense condensates (liquid droplets) and a diluted phase. Over time, these liquid droplets can be transformed into solid aggregates. Bacterial MLOs, containing one dominant component or hundreds of cytoplasmic proteins, have been shown to be involved in various processes, including replication, transcription, cell division, and stress tolerance. The protective function of bacterial MLOs involves sequestration and protection of proteins and RNA from irreversible inactivation or degradation, upregulation of molecular chaperones, and induction of a dormant state. This protective role is particularly significant in the case of pathogenic bacteria exposed to antibiotic therapy. In a dormant state triggered by protein aggregation, pathogens can survive antibiotic therapy as persisters and, after resuming growth, can cause recurrent infections. Recent research has explored the potential use of bacterial MLOs as nanoreactors that catalyze biochemical reactions or serve as protein reservoirs and biosensors, highlighting their potential in biotechnology.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"73-112"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958311","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