{"title":"Transforming Medicine: Advances in Gene Therapy, Immunotherapy, and Targeted Cures.","authors":"Komal Gupta, Vikram Sharma, Tohfa Siddiqui","doi":"10.2174/0113892037336137250102104842","DOIUrl":"10.2174/0113892037336137250102104842","url":null,"abstract":"<p><p>In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes. In pharmaceuticals, gene therapy holds immense potential for addressing genetic disorders, offering a personalized approach to medicine. Immunotherapy, on the other hand, harnesses the body's immune system to combat diseases, including tumors, by enhancing immune responses or directly targeting malignant cells. RNA-based therapeutics have gained prominence due to their ability to modulate gene expression, offering targeted and precise interventions for a wide range of diseases. Cell-based therapies involve the transplantation or manipulation of cells to restore or enhance their function, offering innovative solutions for diseases such as neurodegenerative disorders and cardiovascular diseases. Furthermore, targeted tumor therapies have revolutionized tumor cure by specifically targeting molecular alterations driving tumor growth and minimizing damage to healthy cells. Overall, these novel therapeutic approaches represent a paradigm shift in medicine, offering tailored and precise interventions with the potential to significantly improve patient outcomes and quality of life.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"436-450"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amanda M A Moura, Jose Tadeu A Oliveira, Daniele O B Sousa, Lucas P Dias, Nadine M S Araujo, Raquel de O Rocha, Tawanny K B Aguiar, Joao M M Neto, Viviane O Silva, Ricardo M Feitosa, Queilane L S G Chaves, Marcio V Ramos, Cleverson D T Freitas
{"title":"Purification, Characterization, and Antimicrobial Activity Against <i>Candida parapsilosis</i> and <i>Staphylococcus aureus</i> of a Highly Stable Type-1 Cystatin from Terminalia catappa L. Seeds.","authors":"Amanda M A Moura, Jose Tadeu A Oliveira, Daniele O B Sousa, Lucas P Dias, Nadine M S Araujo, Raquel de O Rocha, Tawanny K B Aguiar, Joao M M Neto, Viviane O Silva, Ricardo M Feitosa, Queilane L S G Chaves, Marcio V Ramos, Cleverson D T Freitas","doi":"10.2174/0113892037339021241017084509","DOIUrl":"10.2174/0113892037339021241017084509","url":null,"abstract":"<p><strong>Introduction: </strong>Clinic infections caused by various microorganisms are a public health concern. The rise of new strains resistant to traditional antibiotics has exacerbated the problem. Thus, the search for new antimicrobial molecules remains highly relevant.</p><p><strong>Methods: </strong>The current study purified, characterized, and assessed the antimicrobial activity of a papain inhibitor from <i>Terminalia catappa</i> L. seeds.</p><p><strong>Results: </strong>The inhibitor was purified by heating the crude extract at 80°C for 30 min, followed by ion exchange chromatography on a DEAE cellulose column. The purification index was 9-fold, yielding 2.3%. SDS-PAGE and size exclusion chromatography revealed that the protease inhibitor (<i>Tc</i>PI) is a 15.9 kDa monomeric protein. The inhibition kinetics showed that <i>Tc</i>PI is a competitive inhibitor specific to papain (Ki = 1.02 x 10<sup>-4</sup> M). <i>Tc</i>PI remained active even after heating at 100oC for 120 min and at pH conditions varying from 2.0 to 10.0. Even after 60 min, <i>Tc</i>PI was resistant to papain proteolysis. <i>Tc</i>PI exhibited antimicrobial activity against <i>Candida parapsilosis</i> and <i>Staphylococcus aureus.</i> Conclusion: Here, we show that <i>Tc</i>PI is a highly stable type-1 cystatin with the potential to combat infections caused by <i>C. parapsilosis</i> and <i>S. aureus</i>. Additional investigations into <i>Tc</i>PI's structural aspects and mechanism of action, as well as safety assessments, are essential prerequisites for its potential application as a novel therapeutic intervention.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"308-319"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Beatriz Leite Nogueira, Filipe de Abreu Vieira, Thalles Barbosa Grangeiro
{"title":"Cysteine Peptidases of <i>Calotropis procera</i> (Apocynaceae): A Literature Review on their Biochemical Properties and Potential Applications.","authors":"Beatriz Leite Nogueira, Filipe de Abreu Vieira, Thalles Barbosa Grangeiro","doi":"10.2174/0113892037340497241024095749","DOIUrl":"10.2174/0113892037340497241024095749","url":null,"abstract":"<p><p>The latex of the xerophytic plant <i>Calotropis procera</i>, popularly known as giant milkweed, contains a complex mixture of secondary metabolites and proteins and has attracted the attention of many researchers. Several bioactive laticifer enzymes from <i>C. procera</i> have been studied for their potential applications in the medical, agricultural and food industries. The present work aimed to review the current scientific knowledge on cysteine peptidases from the latex of this plant, highlighting their biochemical properties and possible uses as biotechnological tools. Bibliographic databases (PubMed, Scopus and Web of Science) were searched for scientific works published in the last six decades reporting the purification, biochemical characterization, molecular cloning and potential applications of laticifer cysteine peptidases from <i>C. procera</i>. Since the first works published in the late 1960s on the occurrence of thiol peptidases in this species, five cysteine peptidases (procerain, procerain B, CpCP-1, CpCP-2 and CpCP-3) have been purified and biochemically characterized. The characterized enzymes are members of the subfamily C1A of sulfhydryl proteases, showing the characteristic biochemical and structural features of papain and related proteins. Several biological activities of the purified enzymes have been demonstrated, including the inhibition of phytopathogenic fungi and milk coagulation properties, which may be of practical use. Moreover, pharmacologically active propeptides released from the posttranslational processing of <i>C. procera</i> cysteine peptidase zymogens have been shown to be promising therapeutic agents against cancer cells. Further research is needed to provide a better comprehensive understanding of the mode of action and biosafety of these molecules.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"296-307"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genomic Analysis of the Caleosin Family in Theaceae Reveals Lineagespecific Evolutionary Patterns.","authors":"Zaibao Zhang, Tao Xiong, Tianyu Fan","doi":"10.2174/0113892037321073240828051039","DOIUrl":"10.2174/0113892037321073240828051039","url":null,"abstract":"<p><strong>Introduction: </strong>Caleosins are recognized as the key proteins found in Lipid Droplets (LDs) and are crucial for the creation, maintenance, and breakdown of LDs. Nevertheless, our understanding of caleosins remains limited within Theaceae, a prominent botanical family encompassing economically significant tea and oil tea species.</p><p><strong>Methods: </strong>In this research, we conducted a comprehensive genome-wide exploration and examination of the caleosin family in Theaceae species with sequenced genomes. The gene number of <i>caleosin</i> was similar among Theaceae species. Segmental duplication was the main form of caleosin expansion in Shuchazao (SCZ), Huangdan (HD), Biyun (BY), Tieguanyin (TGY), Longjing (LJ), <i>C. lanceoleosa</i> (Cla) and <i>C. chekiangoleosa</i> (CCH). Synteny analysis revealed one-to-more and more-to-one collinear relationships of caleosin genes among Theaceae species.</p><p><strong>Results: </strong>Caleosins in Theaceae are categorized into either the H-family or the L-family, each exhibiting distinct motif structures and physicochemical properties. Expression analysis revealed an apparent flower-predominant expression pattern of <i>caleosin</i> genes in Theaceae species. In addition, most paralogous pairs displayed expression divergence.</p><p><strong>Conclusion: </strong>This research enhanced our understanding of the lineage-specific evolution of <i>caleosin</i> genes in Theaceae, and is valuable for future functional analysis of this gene family in tea and oil-tea species.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"139-155"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Farshid Belani, Maryam Mehrabi, Hadi Adibi, Masomeh Mehrabi, Reza Khodarahmi
{"title":"Discovery of Sulfanilamide-diazo Derivatives Incorporating Benzoic Acid Moieties as Novel Inhibitors of Human Carbonic Anhydrase II Activity.","authors":"Farshid Belani, Maryam Mehrabi, Hadi Adibi, Masomeh Mehrabi, Reza Khodarahmi","doi":"10.2174/0113892037332139241008054602","DOIUrl":"10.2174/0113892037332139241008054602","url":null,"abstract":"<p><strong>Background: </strong>Sulfonamides are widely used carbonic anhydrase inhibitors (CAIs) in clinical settings, however, their nonspecific inhibition of multiple carbonic anhydrase isoforms can lead to reduced efficacy and side effects. This study aimed to develop sulfanilamide-diazo derivatives incorporating benzoic acid moieties as novel inhibitors of hCA II activity to reduce side effects and enhance selectivity for different CA isozymes.</p><p><strong>Methods: </strong>We investigated the interaction between these derivatives and the hCA II isozyme via various spectroscopic and docking methods.</p><p><strong>Results: </strong>The kinetic data demonstrates that compound 1 (C1) and compound 2 (C2) share a similar inhibitory strength against hCA II, effectively inhibiting its esterase activity through a noncompetitive mechanism with Ki values at low micromolar levels. Fluorescence measurements indicated that the synthesized compounds suppressed the inherent fluorescence of hCA II via a static quenching process, with each compound showing a singular binding site within the enzyme. Thermodynamic evidences highlight the significance of van der Waals interactions and hydrogen bonding in the binding process. The results of molecular docking indicated that both C1 and C2 effectively obstruct the entrance to hCA II's active site, with no significant differences in their binding conformations.</p><p><strong>Conclusion: </strong>While C1 and C2 exhibit CA inhibitory potency lower than that of sulfonamide compounds, this study offers valuable insights that could pave the way for the development of a promising scaffold for designing new carbonic anhydrase inhibitors.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"226-240"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>In-vitro, In-silico</i> Investigations Reveals Potential Cytotoxic Activity of Fermentation Metabolites from Actinomycetes Isolated from Lonar Soda Lake Against HeLa Cancer Cell Lines.","authors":"Pradip Bawane, Santosh Yele","doi":"10.2174/0113892037334392241216074545","DOIUrl":"10.2174/0113892037334392241216074545","url":null,"abstract":"<p><strong>Background: </strong>Actinomycetes, Gram-positive bacteria, are recognized for producing bioactive metabolites. Lonar Soda Lake, an alkaline ecosystem, hosts diverse actinomycetes with possible anticancer activities.</p><p><strong>Aim: </strong>To assess the cytotoxic potential of fermentation metabolites from actinomycetes isolated from Lonar Soda Lake against HeLa cancer cells employing <i>in-vitro</i> and <i>in-silico</i> methods.</p><p><strong>Objectives: </strong>Evaluate the cytotoxicity of fermentation metabolites from Lonar Lake actinomycetes on HeLa cells. Execute molecular docking to forecast metabolite connections with cancer-related proteins.</p><p><strong>Materials and methods: </strong>The actinomycetes were isolated from the sediment sample of Lonar Lake using a selective medium and recognized by gene sequencing. Cytotoxicity on HeLa cells was assessed using the MTT assay, in consort with oxidative stress and apoptotic markers (GSH, MDA, TNF-α, and caspase 3). Molecular docking and molecular dynamics studies evaluated metabolite binding to cancer-related proteins (Bcl-2, TNF-α, caspase 3).</p><p><strong>Results: </strong>Fermentation metabolites of three Lonar Lake Sediment isolates (LLSD), LLSD-5, LLSD- 7, and LLSD-9 showing promising cytotoxic activity against HeLa cell lines by MTT assay, also significantly modulate the oxidative stress parameters (GSH, MDA), and cell apoptotic marker (TNF-α, caspase 3). IC<sub>50</sub> values were 34.17 μM (LLSD-5), 53.85 μM (LLSD-7), and 69.54 μM (LLSD-9). Furthermore, molecular docking displayed robust binding affinities to cancer-related proteins, uncovering the possible mechanism of action.</p><p><strong>Conclusion: </strong>The fermentation metabolites actinomycete isolates from Lonar Lake exhibit significant cytotoxic activity against HeLa cancer cell lines. Both <i>in-vitro</i> and <i>in-silico</i> analyses support the potential of these metabolites as anticancer agents.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"378-391"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142946114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diet-induced Obesity: Pathophysiology, Consequences and Target Specific Therapeutic Strategies.","authors":"Munmun Banerjee, Veda P Pandey","doi":"10.2174/0113892037329528240827180820","DOIUrl":"10.2174/0113892037329528240827180820","url":null,"abstract":"<p><p>Diet has emerged as a pivotal factor in the current time for diet-induced obesity (DIO). A diet overloaded with fats and carbohydrates and unhealthy dietary habits contribute to the development of DIO through several mechanisms. The prominent ones include the transition of normal gut microbiota to obese microbiota, under-expression of AMPK, and abnormally high levels of adipogenesis. DIO is the root of many diseases. The present review deals with various aspects of DIO and its target proteins that can be specifically used for its treatment. Also, the currently available treatment strategies have been explored. It was found that the expression of five proteins, namely, PPARγ, FTO, CDK4, 14-3-3 ζ protein, and Galectin-1, is upregulated in DIO. They can be used as potential targets for drug-designing studies. Thus, with these targets, the treatment strategy for DIO using natural bioactive compounds can be a safer alternative to medications and bariatric surgeries.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"113-124"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Advances in Migraine Treatment: A Comprehensive Clinical Review.","authors":"Rapuru Rushendran, Chitra Vellapandian","doi":"10.2174/0113892037329429241123095325","DOIUrl":"10.2174/0113892037329429241123095325","url":null,"abstract":"<p><p>Migraine is a neurological disease that, while not inherently causing \"chronic headaches,\" can evolve into a chronic condition over time including major symptoms such as nausea, and light, sound, and allodynia, particularly in cases of frequent episodic migraine or due to factors such as medication overuse or inadequate management. This condition's complex pathophysiology makes treatment difficult. Genetics, trigeminovascular system activation, and cortical spreading depression are involved. Epidemiological research estimates that one in seven persons worldwide are affected, mostly women. Migraine prevalence has increased dramatically in recent decades; however, it varies by demographic and location. This review covers pharmaceutical and non-pharmacological migraine therapy methods and their future. Second-generation triptans have reduced side effects and administration issues, however, Zolmitriptan and Sumatriptan still treat migraines. Monoclonal antibodies that target calcitonin gene-related peptides may prevent migraines; however, their accessibility and safety are problems. Antiepileptics, beta-blockers, and neuromodulation devices are also available. Wearable technology offers customized monitoring and intervention. Precision medicine and gene-based medicines provide hope for tailored migraine treatments, but access, privacy, and informed consent raises ethical concerns. Stakeholder engagement must promote patient autonomy and well-being, responsible implementation, and equal access to novel therapies. A holistic and multidisciplinary approach is needed to manage migraines, taking into consideration present and future therapy developments and new challenges. Research, collaboration, and ethics can improve migraine outcomes and quality of life.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"422-435"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Naiara Macedo Tavares, Micaela de Melo Cordeiro Eulalio, Hallison Mota Santana, Charles Nunes Boeno, Valdison Pereira Dos Reis, Cristina Matiele Alves Rego, Alex Augusto Ferreira E Ferreira, Mauro Valentino Paloschi, Andreimar M Soares, Consuelo Latorre Fortes-Dias, Sulamita Silva Setúbal, Juliana Pavan Zuliani
{"title":"Myotoxicity of Crotoxin on C2C12 Myoblasts and its Inhibition by <i>Crotalus</i> Neutralizing Factor <i>versus</i> Enhanced Resistance in Myotubes: Exploring Toxicity and Membrane Potential.","authors":"Maria Naiara Macedo Tavares, Micaela de Melo Cordeiro Eulalio, Hallison Mota Santana, Charles Nunes Boeno, Valdison Pereira Dos Reis, Cristina Matiele Alves Rego, Alex Augusto Ferreira E Ferreira, Mauro Valentino Paloschi, Andreimar M Soares, Consuelo Latorre Fortes-Dias, Sulamita Silva Setúbal, Juliana Pavan Zuliani","doi":"10.2174/0113892037317894240926081324","DOIUrl":"10.2174/0113892037317894240926081324","url":null,"abstract":"<p><strong>Background: </strong><i>Crotalus</i> Neutralizing Factor (CNF) is a γ-type Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) inhibitor present in the blood of <i>Crotalus durissus terrificus</i> snake. Particularly, CNF inhibits the toxic action of Crotoxin (CTX), which is a major neurotoxin found in <i>C. d. terrificus</i> venom. CTX induces also myotoxic action and demonstrates high selectivity for skeletal muscle fibers. Consequently, CTX can diffuse beyond the site of infection, which can potentially evoke rhabdomyolysis. The present study has evaluated the effects of CTX on myoblasts and myotubes of muscle cells C2C12 <i>in vitro</i> and the effect of CNF on CTX-induced damage.</p><p><strong>Methods: </strong>Cytotoxicity assays were performed by measuring the mitochondrial enzyme dehydrogenase levels. Furthermore, creatine kinase and lactate dehydrogenase levels were used as indicators of muscle damage.</p><p><strong>Results: </strong>Crotoxin has been found to have cytotoxic effects on C2C12 myoblast cells, while CNF has not shown toxic effects on these cells. Furthermore, the findings have shown CNF (50 μg/mL) to abolish CTX toxicity in myoblasts. The myotubes, differentiated cells, showed no change in mitochondrial respiration when exposed to CNF or CTX, showing greater resistance to the toxic actions of crotoxin.</p><p><strong>Conclusion: </strong>The data have confirmed the potential of CNF as an anti-myotoxic agent to prevent CTX-damaged myoblasts and increase resistance to the toxic effects of crotoxin on differentiated cells.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"352-364"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hakan Alici, Vladimir N Uversky, David E Kang, Junga Alexa Woo, Orkid Coskuner-Weber
{"title":"Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10.","authors":"Hakan Alici, Vladimir N Uversky, David E Kang, Junga Alexa Woo, Orkid Coskuner-Weber","doi":"10.2174/0113892037335036241007043530","DOIUrl":"10.2174/0113892037335036241007043530","url":null,"abstract":"<p><strong>Introduction: </strong>The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10<sup>Q108P</sup> proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.</p><p><strong>Methods: </strong>This study presents the foundational characterization of the structural features of CHCHD10<sup>Q108P</sup> and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.</p><p><strong>Results: </strong>Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.</p><p><strong>Conclusion: </strong>The reported structural properties hold promise for informing the development of more effective treatments for ALS.</p>","PeriodicalId":10859,"journal":{"name":"Current protein & peptide science","volume":" ","pages":"201-212"},"PeriodicalIF":1.9,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}