Review
Biochemistry & Molecular Biology
Belen Proano, Julia Casani-Cubel, Maria Benlloch, Ana Rodriguez-Mateos, Esther Navarro-Illana, Jose Maria Lajara-Romance, Jose Enrique de la Rubia Orti
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with no medical cure. Dutasteride, a potential treatment molecule, has shown neuroprotective, antioxidant, and anti-inflammatory effects in ALS.
Review
Immunology
Zongzhi Jiang, Ziyi Wang, Xiaojing Wei, Xue-Fan Yu
Summary: This review article summarizes the role and application of inflammatory markers in amyotrophic lateral sclerosis (ALS). Inflammatory molecules and proteins play a key role in the pathogenesis of ALS and may serve as indicators for predicting patient survival and evaluating treatment response. Furthermore, inflammatory markers have the potential to be used as new therapeutic targets and strategies to expand the therapeutic interventions for ALS.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ines Maestro, Laura R. de la Ballina, Gracia Porras, Silvia Corrochano, Eva De Lago, Anne Simonsen, Patricia Boya, Ana Martinez
Summary: Mitophagy is the process of selectively degrading mitochondria through autophagy, which prevents the accumulation of dysfunctional mitochondria and cellular degeneration. It is known to be altered in neurodegenerative diseases such as ALS. A new mitophagy inhibitor, IGS2.7, was identified and found to restore autophagy to normal levels in ALS models with mutations in SOD1 and TARDBP. This finding suggests a potential therapeutic approach for familial ALS patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Agustina Lara, Ivan Esperante, Maria Meyer, Philippe Liere, Noelia Di Giorgio, Michael Schumacher, Rachida Guennoun, Gisella Gargiulo-Monachelli, Alejandro Federico De Nicola, Maria Claudia Gonzalez Deniselle
Summary: The study on the efficacy of testosterone in the ALS animal model Wobblers mice found that testosterone treatment can alleviate inflammatory responses in the degenerating spinal cord, protect neurons, slow down disease progression, and improve motor performance.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Pavlina Hemerkova, Martin Valis
Summary: ALS is a neurodegenerative disease that affects motor neurons and currently has no cure. Free oxygen radicals are known to play a role in the pathogenesis of ALS, while antioxidant enzymes like SOD1 are crucial for antioxidant protection.
Article
Oncology
Qinming Zhou, Lu He, Jin Hu, Yining Gao, Dingding Shen, You Ni, Yuening Qin, Huafeng Liang, Jun Liu, Weidong Le, Sheng Chen
Summary: The role of CORO1A in ALS pathogenesis was discovered, potentially affecting the disease onset and progression by blocking autophagic flux. Therefore, CORO1A might be a potential biomarker and therapeutic target for ALS.
FRONTIERS OF MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Davide Bassani, Matteo Pavan, Stephanie Federico, Giampiero Spalluto, Mattia Sturlese, Stefano Moro
Summary: This article provides an overview of the role of G protein-coupled receptors (GPCRs) in the onset and progression of amyotrophic lateral sclerosis (ALS), offering useful information and insights. This is of great importance for scientists worldwide in the fight against this disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Correction
Multidisciplinary Sciences
Toru Yamashita, Yoshihiro Kushida, Shohei Wakao, Koh Tadokoro, Emi Nomura, Yoshio Omote, Mami Takemoto, Nozomi Hishikawa, Yasuyuki Ohta, Mari Dezawa, Koji Abe
Summary: The amended version of this paper has been published and can be accessed through a link at the top of the paper.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Mireia Herrando-Grabulosa, Nuria Gaja-Capdevila, Jose M. Vela, Xavier Navarro
Summary: ALS is an adult disease with poor prognosis and no effective cure. The pathogenic mechanisms involved include glutamate excitotoxicity, mitochondrial alterations, and inflammation.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Kazuo Sugimoto, Jia Liu, MingXuan Li, YueBo Song, Chi Zhang, ZhiGuang Zhai, Ying Gao
Summary: The study found that treatment with SFI in the ALS mouse model efficiently postponed disease onset and extended overall survival by reducing motor neuron loss and astrocytic activation in the brain, which was associated with decreasing malondialdehyde level and increasing antioxidant enzyme levels such as superoxide dismutase, Nrf2, heme oxygenase-1, and glutathione S-transferase.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Cell Biology
Alejandro F. De Nicola, Maria Meyer, Laura Garay, Maria Sol Kruse, Michael Schumacher, Rachida Guennoun, Maria Claudia Gonzalez Deniselle
Summary: Progesterone plays a crucial role in neuroprotection by improving neuropathology in the Wobbler mouse model, including reducing motoneuron vacuolization, enhancing mitochondrial respiratory complex activity, and decreasing nitric oxide synthase activity. Additionally, progesterone has differential effects on glial cells, such as increasing oligodendrocyte density and decreasing astrogliosis. These changes are associated with reduced expression of anti-inflammatory markers.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2022)
Article
Cell Biology
Asmita Gyawali, Sana Latif, Seung-Hye Choi, Seung Jae Hyeon, Hoon Ryu, Young-Sook Kang
Summary: In this study, the expression of MCT1 and SMCT1 was found to be altered in ALS cell and mouse models. Valproic acid (VPA) exhibited a neuroprotective effect in different cell lines regardless of MCT dysfunction. These findings could contribute to the development of effective therapeutic strategies for ALS.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Review
Clinical Neurology
Xiaoting Zheng, Shichan Wang, Jingxuan Huang, Junyu Lin, Tianmi Yang, Yi Xiao, Qirui Jiang, Rui Huang, Chunyu Li, Huifang Shang
Summary: Vigorous physical activity, occupational-related activity, leisure time activity, unclassified PA, and professional athletes were associated with a higher risk of developing ALS, while sport-related activity showed no association with ALS.
JOURNAL OF NEUROLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kiyoung Kim
Summary: ALS is a rare neurological disorder characterized by a deficiency in the antioxidant tripeptide glutathione (GSH). Imbalanced GSH homeostasis and its molecular characteristics play crucial roles in ALS development. Studies have shown that GSH metabolism and redox status are associated with neuronal toxicity in ALS.
Article
Multidisciplinary Sciences
Aude Chiot, Shanu F. Roemer, Lisa Ryner, Alina Bogachuk, Katie Emberley, Dillon Brownell, Gisselle A. Jimenez, Michael Leviten, Randall Woltjer, Dennis W. Dickson, Lawrence Steinman, Bahareh Ajami
Summary: This study found that alpha 5 integrin is prominently expressed in motor pathways and perivascular zones associated with the blood-brain barrier in ALS patients and mouse models. Treatment with an antibody against alpha 5 integrin improved survival and motor function in the mouse model.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Computer Science, Artificial Intelligence
Jianfeng Cui, Lixin Wang, Xiangmin He, Victor Hugo C. De Albuquerque, Salman A. AlQahtani, Mohammad Mehedi Hassan
Summary: Feature extraction plays a crucial role in arrhythmia classification. This paper presents a feature extraction method that combines traditional approaches and 1D-CNN to improve the accuracy of arrhythmia classification. Experimental results show that the proposed method achieves an average classification accuracy of 98.35%, surpassing the latest methods.
NEURAL COMPUTING & APPLICATIONS
(2023)
Article
Plant Sciences
Maria Batool, Ali Mahmoud El-Badri, Muhammad Umair Hassan, Yang Haiyun, Wang Chunyun, Yan Zhenkun, Kuai Jie, Bo Wang, Guangsheng Zhou
Summary: Drought poses serious threats to global crop production, including oilseed crops like Brassica napus L. Various approaches have been used to increase drought tolerance, but there is room for further improvement. Future research should focus on developing genetically engineered rapeseed plants with enhanced drought tolerance.
JOURNAL OF PLANT GROWTH REGULATION
(2023)
Article
Biochemistry & Molecular Biology
Bader Saud Alotaibi, Jatin Joshi, Mohammad Raghibul Hasan, Mohd Shahnawaz Khan, Salem Hussain Alharethi, Taj Mohammad, Fahad A. Alhumaydhi, Abdelbaset Mohamed Elasbali, Md Imtaiyaz Hassan
Summary: In this study, potential inhibitors of ROCK1 were identified through structure-based virtual screening of natural compounds. Isoononin and Candidissiol showed appreciable binding affinity and selectivity towards ROCK1, and molecular dynamics simulations confirmed their stability.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Biochemistry & Molecular Biology
Rashid Waseem, Anas Shamsi, Tanzeel Khan, Ayesha Anwer, Mohammad Shahid, Syed Naqui Kazim, Md. Imtaiyaz Hassan, Asimul Islam
Summary: This study monitored the formation of advanced glycation end products (AGEs) and aggregates of irisin, a clinically important protein, induced by methyl-glyoxal (MG). The results suggest that glycation of irisin leads to aggregation, and high levels of MG may contribute to reduced irisin levels in pathological conditions such as obesity, diabetes, and neurological disorders.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Article
Chemistry, Physical
Rashid Waseem, Neetu Singh Yadav, Tanzeel Khan, Faizan Ahmad, Syed Naqui Kazim, Md Imtaiyaz Hassan, Amresh Prakash, Asimul Islam
Summary: In this study, urea-induced denaturation was used to investigate the conformational changes of irisin. The results showed that the unfolding of irisin occurs in a biphasic manner, with an intermediate state (I) populated at 2.5 M urea concentration. Molecular dynamics (MD) simulations confirmed the presence of a molten globule state during the unfolding process of irisin.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Article
Endocrinology & Metabolism
Deepanshi Vijh, Md. Ali Imam, Mohd Maksuf Ul Haque, Subhajit Das, Asimul Islam, Md. Zubbair Malik
Summary: A network pharmacology approach was used to predict the potential protein targets of curcumin in Alzheimer's disease (AD), and identified five key genes through correlation analysis and molecular docking. This study provides novel insights into the therapeutic mechanisms of curcumin and contributes to the clinical application of curcumin for the treatment of AD.
METABOLIC BRAIN DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Shivani Batra, Shagufta Jahan, Anam Ashraf, Bandar Alharby, Talha Jawaid, Asimul Islam, Imtaiyaz Hassan
Summary: Cyclin-dependent kinase 5 (CDK5) is a serine/threonine-directed kinase primarily found in the brain that plays a crucial role in the development of the central nervous system. Recent research has shown that CDK5 is activated by specific cyclins, which regulate its expression and activity. This review examines the role of CDK5 in neurons, synaptic plasticity, DNA damage repair, and the cell cycle, highlighting its therapeutic potential as a target for neurodegenerative diseases. The structural features of CDK5 and its binding with designed inhibitors are also discussed, providing insights for the development of attractive strategies in therapeutic targeting.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Shahnawaz Ahmad, Dinesh Gupta, Tanzeel Ahmed, Asimul Islam
Summary: Human ATP-binding cassette superfamily G member 2 (ABCG2) protein is responsible for multidrug resistance (MDR) in cancerous cells. Utilizing the tetrahydro-beta-carboline (TH beta C) compound library, a new library of TH beta C derivatives was designed based on 3D-QSAR modeling and molecular docking. This study provides new insight for the development of better antagonists against MDR in treating breast cancer.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Manzar Alam, Sarfraz Ahmed, Mohammad Abid, Gulam Mustafa Hasan, Asimul Islam, Md. Imtaiyaz Hassan
Summary: Microtubule affinity-regulating kinase 4 (MARK4) is a crucial protein kinase involved in the development of cancer and neurodegenerative diseases. It modulates various signaling pathways and has potential as a drug target for cancer, diabetes, and Alzheimer's. However, there is limited knowledge on its structure, function, and clinical significance. This review provides detailed information on MARK4's structure, role in signaling pathways, and therapeutic potential as well as updates on its research, which will aid in the development of effective therapeutic molecules.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2023)
Review
Nutrition & Dietetics
Md. Khabeer Azhar, Saleha Anwar, Gulam Mustafa Hasan, Anas Shamsi, Asimul Islam, Suhel Parvez, Md. Imtaiyaz Hassan
Summary: Rosmarinic acid (RA) is an abundant phytochemical with anti-inflammatory and antioxidant properties, playing significant roles in cancer, neuroprotection, and diabetes.
Article
Biochemistry & Molecular Biology
Deeba Shamim Jairajpuri, Taj Mohammad, Afzal Hussain, Samira Amir, Urooj Fatima, Mohamed F. AlAjmi, Dharmendra Kumar Yadav, Md. Imtaiyaz Hassan
Summary: This study explored the potential of phytoconstituents as inhibitors of ALK1 using virtual screening and molecular dynamics simulations. Candidine, a phytoconstituent, showed high affinity and specific interactions with the ALK1 active site, stabilizing its structure.
JOURNAL OF MOLECULAR RECOGNITION
(2023)
Article
Engineering, Civil
Xiaoding Wang, Sahil Garg, Hui Lin, Georges Kaddoum, Jia Hu, Mohammad Mehedi Hassan
Summary: This paper proposes a hierarchical trust evaluation strategy based on heterogeneous blockchain, utilizing federated deep learning technology for Intelligent Transportation Systems (ITS) security.
IEEE TRANSACTIONS ON INTELLIGENT TRANSPORTATION SYSTEMS
(2023)
Article
Education & Educational Research
Faizan Ahmad, Luo Zongwei, Zeeshan Ahmed, Sara Muneeb
Summary: This paper presents an empirical study on the experiences of players during brain games play, analyzing correlations among different types of experiences and identifying similarities and differences among different age groups. The observations provide insights to predict players' behavioral trends and simplify the user feedback process.
INTERACTIVE LEARNING ENVIRONMENTS
(2023)
Article
Chemistry, Medicinal
Shuang Mei, Su Jiang, Yuting Wang, Han Jing, Peng Yang, Miao-Miao Niu, Jindong Li, Kai Yuan, Yan Zhang
Summary: This study identifies a dual-targeting peptide, AP-1, that effectively inhibits variants of concern (VOCs) of SARS-CoV-2 without impairing host cell viability. The findings suggest that AP-1 could be a promising broad-spectrum agent for treating emerging VOCs of SARS-CoV-2.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Hyeonjun Lee, Ju Yeon Lee, Hyunsoo Jang, Hye Young Cho, Minhee Kang, Sang Hyun Bae, Suin Kim, Eunji Kim, Jaebong Jang, Jin Young Kim, Young Ho Jeon
Summary: By using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance experiments, we identified new chemical moieties that bind to the target sites of the protein of interest, allowing for reversible binding and protein degradation. This method has the potential to expand the application of PROTAC technology.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Yingying Li, Xiyou Du, Xinru Kong, Yuelin Fang, Zhijing He, Dongzhu Liu, Hang Wu, Jianbo Ji, Xiaoye Yang, Lei Ye, Guangxi Zhai
Summary: This study proposes a novel nanoplatform based on the autophagy cascade to overcome the obstacles in chemo-immunotherapy. The platform combines chemotherapy and starvation therapy to initiate pro-death autophagy and enhance antigen presentation, while also remodeling the immunosuppressive tumor microenvironment. Furthermore, the study discovers a new therapeutic direction for the respiration inhibitor 3-bromopyruvic acid (3BP) in cancer treatment. Overall, this study offers an opportunity to improve antitumor efficacy and boost immune responses.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Bingsi Wang, Mingxu Ma, Yusen Dai, Pengfei Yu, Liang Ye, Wenyan Wang, Chunjie Sha, Huijie Yang, Yingjie Yang, Yunjing Zhu, Lin Dong, Shujuan Wei, Linlin Wang, Jingwei Tian, Hongbo Wang
Summary: Breast cancer is a common malignant tumor in women, and drug resistance remains a clinical challenge. In this study, a novel compound, G-5b, was developed with potent antagonistic and degradation activities comparable to the current drug fulvestrant. G-5b also showed improved stability and solubility. Mechanistically, G-5b engages the proteasome pathway to degrade ER, inhibiting the ER signaling pathway and inducing apoptosis and cell cycle arrest. In animal models, G-5b exhibited superior pharmacokinetics and pharmacodynamics properties. Overall, G-5b is a promising long-acting SERD worthy of further investigation and optimization.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Karoline B. Waitman, Larissa C. de Almeida, Marina C. Primi, Jorge A. E. G. Carlos, Claudia Ruiz, Thales Kronenberger, Stefan Laufer, Marcia Ines Goettert, Antti Poso, Sandra V. Vassiliades, Vinicius A. M. de Souza, Monica F. Z. J. Toledo, Neuza M. A. Hassimotto, Michael D. Cameron, Thomas D. Bannister, Leticia Costa-Lotufo, Joa o A. Machado-Neto, Mauricio T. Tavares, Roberto Parise-Filho
Summary: A series of hybrid inhibitors combining pharmacophores of known kinase inhibitors and benzohydroxamate HDAC inhibitors were synthesized and evaluated for their anticancer activity and pharmacokinetic properties. Compounds 4d-f exhibited promising cytotoxicity against hematological cells and moderate activity against solid tumor models. Compound 4d showed potent inhibition of multiple kinase targets and had stable interactions with HDAC and members of the JAK family. These compounds showed selective cytotoxicity with minimal effects on non-tumorigenic cells and favorable pharmacokinetic profiles.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Michal Sulik, Diana Fontinha, Dietmar Steverding, Szymon Sobczak, Michal Antoszczak, Miguel Prudencio, Adam Huczynski
Summary: This study describes the synthesis of the first-in-class ivermectin derivatives obtained through derivatization of the C13 position, along with the unexpected rearrangement of the macrolide ring. These derivatives show potential for antiparasitic activity and are important for the development of new antiparasitic agents.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Jun Liu, Qiu-Xian Chen, Wen-Fu Wu, Dong Wang, Si -Yu Zhao, Jia-Hao Li, Yi-Qun Chang, Shao-Gao Zeng, Jia-Yi Hu, Yu-Jie Li, Jia-Xin Du, Shu-Meng Jiao, Hai-Chuan Xiao, Qiang Zhang, Jun Xu, Jian-Fu Zhao, Hai -Bo Zhou, Yong-Heng Wang, Jian Zou, Ping-Hua Sun
Summary: A new anti-infective drug strategy has been discovered to attenuate virulence and modulate inflammation caused by drug-resistant Pseudomonas aeruginosa infections. Compound 5f inhibits biofilm formation, macrophage migration, and inflammatory response induced by P. aeruginosa, showing potential as a novel candidate against drug-resistant infections.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Liuzeng Chen, Ke Wang, Lingyun Wang, Wei Wang, Lifan Wang, Jia Li, Xiaohan Liu, Mengya Wang, Banfeng Ruan
Summary: In this study, a series of novel anti-inflammatory compounds were designed and synthesized based on the natural product pterostilbene skeleton. Among them, compound 8 showed the highest activity and exhibited its effects through inhibition of pro-inflammatory cytokines by blocking the NF-KB/MAPK signaling pathway. Compound 8 also demonstrated a good relieving effect on acute colitis in mice and showed good safety in acute toxicity experiments.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)
Article
Chemistry, Medicinal
Si-Min Liang, Gui-Bin Liang, Hui-Ling Wang, Hong Jiang, Xian-Li Ma, Jian-Hua Wei, Ri-Zhen Huang, Ye Zhang
Summary: A series of novel multi-target antitumor agents were designed, synthesized, and evaluated. Some compounds exhibited significant antitumor activity and one compound showed excellent efficacy, limited toxicity, and low resistance. Further mechanism studies revealed that the compound exerted antitumor effects through multiple pathways.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2024)