Advances in protein chemistry and structural biology最新文献

{"title":"The role of mitochondria and mitophagy in cell senescence.","authors":"Tayyab Ali,&nbsp;Fatma Hussain,&nbsp;Haroon Ur Rashid Kayani,&nbsp;Muhammad Naeem,&nbsp;Fozia Anjum","doi":"10.1016/bs.apcsb.2023.03.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.03.001","url":null,"abstract":"<p><p>Mitochondrial malfunction and cell senescence have been defined as the hallmarks of aging. Cell senescence leads to the loss of health allied with aging. While deciphering the complex association between mitochondria and cellular senescence, it is observed that senescence has a two-faced nature being beneficial and hazardous. This duality of cellular senescence is associated with circumstantial aspects. During the process of cellular senescence, dysfunctional mitochondria are accumulated, the efficiency of the oxidative phosphorylation process declines along with the enhanced synthesis of reactive oxygen species. It is suggested that reduction in the negative consequences of senescence throughout old age might be accomplished by targeting the mitochondria as all roads lead towards mitochondria. It is unclear how perturbation of mitophagy in senescence results in the accumulation of mitochondria, impairment of mitochondrial biogenesis and onset of diseases. Understanding this complex interplay will bring about a long yet healthy lifespan. But definitely casual and specific players contribute in the initiation and conservation of the cell senescence. Variations in metabolism, quality control and dynamics of mitochondria are observed during cell aging process. Several On-target and Off-target mechanisms can also cause side effects in cellular senescence. Translational research of these mechanisms may lead to effective clinical interventions. This chapter reviews the role of mitochondria, homeostatic mechanisms and mitophagy as drivers and effectors of cell senescence along with multiple signalling pathways that lead to the initiation, maintenance, induction and suppression of cellular aging process during health and disease.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"136 ","pages":"93-115"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219874","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":"Phytotherapeutic targeting of the mitochondria in neurodegenerative disorders.","authors":"Priyanka Sarkar,&nbsp;Ashish Kumar,&nbsp;Partha Sarathi Behera,&nbsp;Kavitha Thirumurugan","doi":"10.1016/bs.apcsb.2023.02.013","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.02.013","url":null,"abstract":"<p><p>Neurodegenerative diseases are characterized by degeneration or cellular atrophy within specific structures of the brain. Neurons are the major target of neurodegeneration. Neurons utilize 75-80% of the energy produced in the brain. This energy is either formed by utilizing the glucose provided by the cerebrovascular blood flow or by the in-house energy producers, mitochondria. Mitochondrial dysfunction has been associated with neurodegenerative diseases. But recently it has been noticed that neurodegenerative diseases are often associated with cerebrovascular diseases. Cerebral blood flow requires vasodilation which to an extent regulated by mitochondria. We hypothesize that when mitochondrial functioning is disrupted, it is not able to supply energy to the neurons. This disruption also affects cerebral blood flow, further reducing the possibilities of energy supply. Loss of sufficient energy leads to neuronal dysfunction, atrophy, and degeneration. In this chapter, we will discuss the metabolic modifications of mitochondria in aging-related neurological disorders and the potential of phytocompounds targeting them.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"136 ","pages":"415-455"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239509","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 secretory phenotypes of envenomed cells: Insights into venom cytotoxicity.","authors":"Y Yong,&nbsp;J J Hiu,&nbsp;M K K Yap","doi":"10.1016/bs.apcsb.2022.08.001","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.08.001","url":null,"abstract":"<p><p>Snake envenomation is listed as Category A Neglected Tropical Diseases (NTD) by World Health Organization, indicates a severe public health problem. The global figures for envenomation cases are estimated to be more than 1.8 million annually. Even if the affected victims survive the envenomation, they might suffer from permanent morbidity due to local envenomation. One of the most prominent local envenomation is dermonecrosis. Dermonecrosis is a pathophysiological outcome of envenomation that often causes disability in the victims due to surgical amputations, deformities, contracture, and chronic ulceration. The key venom toxins associated with this local symptom are mainly attributed to substantial levels of enzymatic and non-enzymatic toxins as well as their possible synergistic actions. Despite so, the severity of the local tissue damage is based on macroscopic observation of the bite areas. Furthermore, limited knowledge is known about the key biomarkers involved in the pathogenesis of dermonecrosis. The current immunotherapy with antivenom is also ineffective against dermonecrosis. These local effects eventually end up as sequelae. There is also a global shortage of toxins-targeted therapeutics attributed to inadequate knowledge of the actual molecular mechanisms of cytotoxicity. This chapter discusses the characterization of secretory phenotypes of dermonecrosis as an advanced tool to indicate its severity and pathogenesis in envenomation. Altogether, the secretory phenotypes of envenomed cells and tissues represent the precise characteristics of dermonecrosis caused by venom toxins.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"133 ","pages":"193-230"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642399","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":"Secretory proteins in the orchestration of microbial virulence: The curious case of Staphylococcus aureus.","authors":"Dileep Francis,&nbsp;Anusha Bhairaddy,&nbsp;Atheene Joy,&nbsp;Gopika Veeramanickathadathil Hari,&nbsp;Ashik Francis","doi":"10.1016/bs.apcsb.2022.10.004","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.10.004","url":null,"abstract":"<p><p>Microbial virulence showcases an excellent model for adaptive changes that enable an organism to survive and proliferate in a hostile environment and exploit host resources to its own benefit. In Staphylococcus aureus, an opportunistic pathogen of the human host, known for the diversity of the disease conditions it inflicts and the rapid evolution of antibiotic resistance, virulence is a consequence of having a highly plastic genome that is amenable to quick reprogramming and the ability to express a diverse arsenal of virulence factors. Virulence factors that are secreted to the host milieu effectively manipulate the host conditions to favor bacterial survival and growth. They assist in colonization, nutrient acquisition, immune evasion, and systemic spread. The structural and functional characteristics of the secreted virulence proteins have been shaped to assist S. aureus in thriving and disseminating effectively within the host environment and exploiting the host resources to its best benefit. With the aim of highlighting the importance of secreted virulence proteins in bacterial virulence, the present chapter provides a comprehensive account of the role of the major secreted proteins of S. aureus in orchestrating its virulence in the human host.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"133 ","pages":"271-350"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10642400","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":"Therapeutic targeting of mitochondria-proteostasis axis by antioxidant polysaccharides in neurodegeneration.","authors":"Qiangqiang Wang,&nbsp;Muhammad Zeeshan Adil,&nbsp;Xiaoliang Xie,&nbsp;Shihao Zhao,&nbsp;Ju Zhang,&nbsp;Zebo Huang","doi":"10.1016/bs.apcsb.2023.02.017","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.02.017","url":null,"abstract":"<p><p>Aging is a major risk factor for many age-associated disorders, including neurodegenerative diseases. Both mitochondrial dysfunction and proteostatic decline are well-recognized hallmarks of aging and age-related neurodegeneration. Despite a lack of therapies for neurodegenerative diseases, a number of interventions promoting mitochondrial integrity and protein homeostasis (proteostasis) have been shown to delay aging-associated neurodegeneration. For example, many antioxidant polysaccharides are shown to have pharmacological potentials in Alzheimer's, Parkinson's and Huntington's diseases through regulation of mitochondrial and proteostatic pathways, including oxidative stress and heat shock responses. However, how mitochondrial and proteostatic mechanisms work together to exert the antineurodegenerative effect of the polysaccharides remains largely unexplored. Interestingly, recent studies have provided a growing body of evidence to support the crosstalk between mitostatic and proteostatic networks as well as the impact of the crosstalk on neurodegeneration. Here we summarize the recent progress of antineurodegenerative polysaccharides with particular attention in the mitochondrial and proteostatic context and provide perspectives on their implications in the crosstalk along the mitochondria-proteostasis axis.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"136 ","pages":"385-413"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9916299","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":"Single nucleotide polymorphisms (SNPs) in circadian genes: Impact on gene function and phenotype.","authors":"Ibrahim Baris,&nbsp;Onur Ozcan,&nbsp;Ibrahim Halil Kavakli","doi":"10.1016/bs.apcsb.2023.03.002","DOIUrl":"10.1016/bs.apcsb.2023.03.002","url":null,"abstract":"<p><p>Circadian rhythm is an endogenous timing system that allows an organism to anticipate and adapt to daily changes and regulate various physiological variables such as the sleep-wake cycle. This rhythm is governed by a molecular circadian clock mechanism, generated by a transcriptional and translational feedback loop (TTFL) mechanism. In mammals, TTFL is determined by the interaction of four main clock proteins: BMAL1, CLOCK, Cryptochromes (CRY), and Periods (PER). BMAL1 and CLOCK form dimers and initiate the transcription of clock-controlled genes (CCG) by binding an E-box element with the promotor genes. Among CCGs, PERs and CRYs accumulate in the cytosol and translocate into the nucleus, where they interact with the BMAL1/CLOCK dimer and inhibit its activity. Several epidemiological and genetic studies have revealed that circadian rhythm disruption causes various types of disease. In this chapter, we summarize the effect of core clock gene SNPs on circadian rhythm and diseases in humans.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"137 ","pages":"17-37"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286693","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":"Changing ROS, NAD and AMP: A path to longevity via mitochondrial therapeutics.","authors":"Oleh Lushchak,&nbsp;Dmytro Gospodaryov,&nbsp;Olha Strilbytska,&nbsp;Maria Bayliak","doi":"10.1016/bs.apcsb.2023.03.005","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2023.03.005","url":null,"abstract":"<p><p>Lifespan of many organisms, from unicellular yeast to extremely complex human organism, strongly depends on the genetic background and environmental factors. Being among most influential target energy metabolism is affected by macronutrients, their caloric values, and peculiarities of catabolism. Mitochondria are central organelles that respond for energy metabolism in eukaryotic cells. Mitochondria generate reactive oxygen species (ROS), which are lifespan modifying metabolites and a kind of biological clock. Oxidized nicotinamide adenine dinucleotide (NAD⁺) and adenosine monophosphate (AMP) are important metabolic intermediates and molecules that trigger or inhibit several signaling pathways involved in gene silencing, nutrient allocation, and cell regeneration and programmed death. A part of NAD⁺ and AMP metabolism is tied to mitochondria. Using substances that able to target mitochondria, as well as allotopic expression of specific enzymes, are envisioned to be innovative approaches to prolong lifespan by modulation of ROS, NAD⁺, and AMP levels. Among substances, an anti-diabetic drug metformin is believed to increase NAD⁺ and AMP levels, indirectly influencing histone deacetylases, involved in gene silencing, and AMP-activated protein kinase, an energy sensor of cells. Mitochondrially targeted derivatives of ubiquinone were found to interact with ROS. A mitochondrially targeted non-proton-pumping NADH dehydrogenase may influence both ROS and NAD⁺ levels. Chapter describes putative how mitochondria-targeted drugs and NADH dehydrogenase extend lifespan, perspectives of creating drugs with similar properties and their usage as senotherapeutic pills are discussed in the chapter.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"136 ","pages":"157-196"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239512","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":"Identification of dysregulated canonical pathways associated with pathogenesis and progression of Amyotrophic Lateral Sclerosis-An integrated bioinformatics approach.","authors":"Ankur Datta,&nbsp;S Udhaya Kumar,&nbsp;Maria D'costa,&nbsp;Anusha Bothe,&nbsp;D Thirumal Kumar,&nbsp;Hatem Zayed,&nbsp;C George Priya Doss","doi":"10.1016/bs.apcsb.2022.11.014","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.11.014","url":null,"abstract":"<p><p>The mechanisms responsible for the pathogenesis and progression of Amyotrophic Lateral Sclerosis (ALS) remain poorly understood, making the diagnosis of ALS challenging. We aimed to find the novel gene biomarkers via computationally analyzing microarray expression studies, in three different cell lineages, namely myotube cells, astrocyte cells and oligodendrocyte cells. Microarray gene expression profiles were obtained and analyzed for three cell types: myotube cell lineage (GSE122261), astrocyte, and oligodendrocyte cell lineage (GSE87385). A comprehensive computational pipeline, tailored explicitly for microarray gene expression profiling studies, was devised to analyze the sample groups, wherein the myotube sample group comprised of six control (GSM3462697, GSM3462698, GSM3462699, GSM3462700, GSM3462701, GSM3462702) & six diseased (GSM3462691, GSM3462692, GSM3462693, GSM3462694, GSM3462695, GSM3462696) samples were considered. Similarly, for the astrocyte sample group two samples each for the control (GSM2330040, GSM2330042) and the diseased (GSM2330039, GSM2330041), and for the oligodendrocyte sample group, 2 control (GSM2330043, GSM2330045) samples and two diseased (GSM2330044, GSM2330046) samples were considered for the current study. The in-depth interaction of these DEGs was studied using MCODE and subjected to preliminary functional analysis using ClueGO/CluePedia plug-in. Qiagen's IPA software was employed for enrichment analysis, which generated the key canonical pathways and a list of potential biomarker molecules specific to each sample group. The preliminary analysis yielded 512 DEGs across all 3-sample groups, wherein 139 DEGs belonged to the myotube sample group, 216 DEGs for the astrocyte sample group, and 157 DEGs for the oligodendrocytes sample group. The data suggests growth hormone signaling and its activity, ErbB signaling pathway, and JAK/STAT signaling pathway are some of the pathways that are significantly dysregulated and play a crucial role in the development and progression of ALS. KISS1R and CSHL1 are potential genes that could act as diagnostic biomarkers in myotube cell types. Also, KRAS, TGFB2, JUN, and SMAD6 genes may be used as prognostic biomarkers to differentiate between early and late-stage ALS-diseased patients.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"134 ","pages":"21-52"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335418","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":"Emerging role of heat shock proteins in cardiovascular diseases.","authors":"Joyita Hazra,&nbsp;Anupama Vijayakumar,&nbsp;Nitish R Mahapatra","doi":"10.1016/bs.apcsb.2022.10.008","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.10.008","url":null,"abstract":"<p><p>Heat Shock Proteins (HSPs) are evolutionarily conserved proteins from prokaryotes to eukaryotes. They are ubiquitous proteins involved in key physiological and cellular pathways (viz. inflammation, immunity and apoptosis). Indeed, the survivability of the cells under various stressful conditions depends on appropriate levels of HSP expression. There is a growing line of evidence for the role of HSPs in regulating cardiovascular diseases (CVDs) (viz. hypertension, atherosclerosis, atrial fibrillation, cardiomyopathy and heart failure). Furthermore, studies indicate that a higher concentration of circulatory HSP antibodies correlate to CVDs; some are even potential markers for CVDs. The multifaceted roles of HSPs in regulating cellular signaling necessitate unraveling their links to pathophysiology of CVDs. This review aims to consolidate our understanding of transcriptional (via multiple transcription factors including HSF-1, NF-κB, CREB and STAT3) and post-transcriptional (via microRNAs including miR-1, miR-21 and miR-24) regulation of HSPs. The cytoprotective nature of HSPs catapults them to the limelight as modulators of cell survival. Yet another attractive prospect is the development of new therapeutic strategies against cardiovascular diseases (from hypertension to heart failure) by targeting the regulation of HSPs. Moreover, this review provides insights into how genetic variation of HSPs can contribute to the manifestation of CVDs. It would also offer a bird's eye view of the evolving role of different HSPs in the modulation and manifestation of cardiovascular disease.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"134 ","pages":"271-306"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335423","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 phosphatases and their targets: Comprehending the interactions in plant signaling pathways.","authors":"Lokesh K Saini,&nbsp;Malathi Bheri,&nbsp;Girdhar K Pandey","doi":"10.1016/bs.apcsb.2022.11.003","DOIUrl":"https://doi.org/10.1016/bs.apcsb.2022.11.003","url":null,"abstract":"<p><p>Protein phosphorylation is a vital reversible post-translational modification. This process is established by two classes of enzymes: protein kinases and protein phosphatases. Protein kinases phosphorylate proteins while protein phosphatases dephosphorylate phosphorylated proteins, thus, functioning as 'critical regulators' in signaling pathways. The eukaryotic protein phosphatases are classified as phosphoprotein phosphatases (PPP), metallo-dependent protein phosphatases (PPM), protein tyrosine (Tyr) phosphatases (PTP), and aspartate (Asp)-dependent phosphatases. The PPP and PPM families are serine (Ser)/threonine (Thr) specific phosphatases (STPs) that dephosphorylate Ser and Thr residues. The PTP family dephosphorylates Tyr residues while dual-specificity phosphatases (DsPTPs/DSPs) dephosphorylate Ser, Thr, and Tyr residues. The composition of these enzymes as well as their substrate specificity are important determinants of their functional significance in a number of cellular processes and stress responses. Their role in animal systems is well-understood and characterized. The functional characterization of protein phosphatases has been extensively covered in plants, although the comprehension of their mechanistic basis is an ongoing pursuit. The nature of their interactions with other key players in the signaling process is vital to our understanding. The substrates or targets determine their potential as well as magnitude of the impact they have on signaling pathways. In this article, we exclusively overview the various substrates of protein phosphatases in plant signaling pathways, which are a critical determinant of the outcome of various developmental and stress stimuli.</p>","PeriodicalId":7376,"journal":{"name":"Advances in protein chemistry and structural biology","volume":"134 ","pages":"307-370"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9335424","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}