Advances in protein chemistry and structural biology最新文献_第10页

Tau PET probes for Alzheimer's disease detection and their structural characterization. Tau PET探针用于阿尔茨海默病检测及其结构表征。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-03-10 DOI: 10.1016/bs.apcsb.2024.10.006

Subashchandrabose Chinnathambi, Sneha Malik, Madhura Chandrashekar

{"title":"Tau PET probes for Alzheimer's disease detection and their structural characterization.","authors":"Subashchandrabose Chinnathambi, Sneha Malik, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2024.10.006","DOIUrl":"10.1016/bs.apcsb.2024.10.006","url":null,"abstract":"There are two hallmarks for the Alzheimer's disease that are currently used to identify the disease- the presence of the proteins Amyloid-β and Tau. Amyloid PET has been studied for a long time and many effective probes have been introduced, some approved by the FDA, including [18F]-florbetaben (Neuraceq), [18F]-florbetapir (Amyvid), [18F]-flutemetamol (Vizamyl). However, it was found that imaging of NFTs could give more accurate results as the accumulation of Tau could directly be correlated with neurodegeneration, which isn't the case for Amyloid-β. Amyloid PET is thereby a diagnostic tool, which can rather be used for confirming the absence of Alzheimer's Disease. Tau PET, which was found to be a potentially useful diagnostic tool was explored further as it can directly be associated with the extent of spread of the disease. This led to the discovery of many probes for Tau PET. The initial ones were non-selective for Tau over Aβ. Further exploration suggested two generations of Tau probes, both with higher selectivity for Tau over Aβ. A second generation was introduced to overcome the shortcomings of the first generation which are examined in this review. Much research on effective Tau PET probes has led to an FDA-approved Tau probe, 18F-flortaucipir. This systematic review discusses the characteristics and effectiveness of the first-generation probes, second-generation probes and other newer probes. It discusses the structural changes made in the probes over time that led to the enhancement of their properties as a Tau probe, that is, increased affinity and selectivity for Tau. It also discusses the shortcomings of probes developed so far and the ideal characteristics for Tau probes.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"145 ","pages":"255-285"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958326","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

Cholesterol metabolism regulates Tauopathy in Alzheimer's disease. 胆固醇代谢调节阿尔茨海默病的tau病变。

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.2024.11.005

Subashchandrabose Chinnathambi, Anusree Adityan, Madhura Chandrashekar

{"title":"Cholesterol metabolism regulates Tauopathy in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Anusree Adityan, Madhura Chandrashekar","doi":"10.1016/bs.apcsb.2024.11.005","DOIUrl":"10.1016/bs.apcsb.2024.11.005","url":null,"abstract":"Cholesterol, produced by astrocytes, is vital for the formation and maintenance of synapse, highlighting the significance of lipid metabolism in neuronal health. Neural stem cells (NSCs) are versatile, self-renewing and capable of differentiating into neurons, astrocytes, and oligodendrocytes, playing a pivotal role in both embryonic development and adult neurogenesis. In the central nervous system (CNS), NSCs primarily reside in the subventricular zone (SVZ) and the sub-granular layer of the dentate gyrus, where they give rise to neural progenitors and subsequently to neurons and glial cells. Oligodendrocytes play a crucial role in the CNS function and myelin sheath formation, which is essential for rapid neuronal signal transmission. Astrocytes contribute to brain homeostasis by regulating lipid metabolism and providing metabolic support to neurons. Sphingolipids and phospholipids are integral to neural cell membrane structure and function, influencing processes such as neurogenesis, cell signaling, and synaptic plasticity. Furthermore, the ApoE4 allele impacts lipid metabolism, affecting the risk of neurodegenerative diseases. This paper explores the role of various cell types and lipids in the CNS, emphasizing the importance of lipid metabolism in maintaining neural function and the implications for neurodegenerative conditions.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"401-421"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090761","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

SUMO inhibits Tau aggregation in Alzheimer's disease. SUMO抑制阿尔茨海默病中的Tau聚集。

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.2025.02.001

Subashchandrabose Chinnathambi, Nagaraj Rangappa

{"title":"SUMO inhibits Tau aggregation in Alzheimer's disease.","authors":"Subashchandrabose Chinnathambi, Nagaraj Rangappa","doi":"10.1016/bs.apcsb.2025.02.001","DOIUrl":"10.1016/bs.apcsb.2025.02.001","url":null,"abstract":"Tau is a microtubule-binding, hydrophilic protein and appears randomly coiled in circular dichroism spectra. Tau can have many post-translational modifications such as phosphorylation, acetylation, SUMOylation, glycation, ubiquitinylation, etc. The abnormal phosphorylation of Tau lowers its affinity to bind the microtubules, causing to neuronal instability. Hyperphosphorylated Tau can get detach from the microtubules and get aggregate in neuronal cell body to form a neurofibrillary tangle, which leads to weaken axonal transport and cause synaptic dysfunction. Tau itself is a SUMO-1 target protein and the modified lysine has been identified as the K340 located within 4R-Tau. The interaction between Tau and SUMO-1 was confirmed by an independent study, by showing that the SUMO-1 immunoreactivity is co-localized with phosphorylated Tau. In addition to this, Tau can also be ubiquitinated and degraded by the proteasome through both ubiquitin-dependent and ubiquitin-independent pathways. Our study shows that SUMOylation at lysine K340 stimulates Tau phosphorylation and inhibits ubiquitination-mediated Tau degradation, thus favouring its aggregation.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"147 ","pages":"355-374"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090900","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

Protein misfolding and unfolded protein response in cancer: Current updates with focus on epigenetic regulation. 癌症中的蛋白质错误折叠和未折叠蛋白质反应：当前更新的重点是表观遗传调控。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-09-29 DOI: 10.1016/bs.apcsb.2025.08.014

Shayista Akbar, Moammir H Aziz, Ludenn Elkhidir, Kirti S Prabhu, Tariq Al-Qirim, Moayad Shahwan, Syed M Hasan Rizvi, Abdul Wahid Ansari, Shahab Uddin, Aamir Ahmad

{"title":"Protein misfolding and unfolded protein response in cancer: Current updates with focus on epigenetic regulation.","authors":"Shayista Akbar, Moammir H Aziz, Ludenn Elkhidir, Kirti S Prabhu, Tariq Al-Qirim, Moayad Shahwan, Syed M Hasan Rizvi, Abdul Wahid Ansari, Shahab Uddin, Aamir Ahmad","doi":"10.1016/bs.apcsb.2025.08.014","DOIUrl":"10.1016/bs.apcsb.2025.08.014","url":null,"abstract":"The structure of proteins holds the key to their optimum functioning. Misfolding of proteins often renders them useless and the resulting aggregates are implicated in endoplasmic reticulum stress and the onset of several human diseases. Therefore, a robust system, spearheaded by unfolded protein response (UPR) is in place as a quality check. The unfolded proteins are cleared and marked for degradation. UPR pathway consists of multiple factors, such as the chaperone GRP78, and is often deregulated in cancers, thus presenting as an attractive target for therapy. Emerging evidence indicates epigenetic regulation of UPR with the involvement of non-coding RNAs, such as, microRNAs and long non-coding RNAs, as well as DNA methylation and histone modifications. Here, we provide an overview of UPR in tumorigenesis with a focus on mutual inter-regulatory relationship between UPR and non-coding RNAs. We also discuss the novel findings on transport of misfolded proteins in exosomes and the promising role of epigenetic drugs in modulation of UPR.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"148 ","pages":"117-134"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627855","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

From antibodies to nanobodies: The next frontier in cancer theranostics for solid tumors. 从抗体到纳米体：实体瘤癌症治疗的下一个前沿。

3区生物学

Advances in protein chemistry and structural biology Pub Date : 2025-01-01 Epub Date: 2025-01-30 DOI: 10.1016/bs.apcsb.2024.10.014

Sanjana Mehrotra, Navdeep Kaur, Sukhpreet Kaur, Kawaljit Matharoo, Rajeev Kumar Pandey

{"title":"From antibodies to nanobodies: The next frontier in cancer theranostics for solid tumors.","authors":"Sanjana Mehrotra, Navdeep Kaur, Sukhpreet Kaur, Kawaljit Matharoo, Rajeev Kumar Pandey","doi":"10.1016/bs.apcsb.2024.10.014","DOIUrl":"10.1016/bs.apcsb.2024.10.014","url":null,"abstract":"The field of cancer therapeutics has witnessed significant advancements over the past decades, particularly with the emergence of immunotherapy. This chapter traces the transformative journey from traditional antibody-based therapies to the innovative use of nanobodies in the treatment and diagnosis of solid tumors. Nanobodies are the smallest fragments of antibodies derived from camelid immunoglobulins and have redefined the possibilities in cancer theranostics due to their unique structural and functional properties. We provide an overview of the biochemical characteristics of nanobodies that make them particularly suitable for theranostic applications, such as their small size, high stability, enhanced infiltration into the complex tumor microenvironment (TME) and ability to bind with high affinity to epitopes that are inaccessible to conventional antibodies. Further, their ease of modification and functionalization has enabled the development of nanobody-based drug conjugates/toxins and radiolabeled compounds for precise imaging and targeted radiotherapy. We elucidate how nanobodies are being served as valuable tools for prognostic assessment, enabling clinicians to predict disease aggressiveness, monitor treatment response, and stratify patients for personalized therapeutic interventions.","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"144 ","pages":"287-329"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466732","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

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

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":"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":"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

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":"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