Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies Ramin Raoufinia, Ghazal Alyari, Amin Tadayoni nia, Mohammad Reza Abbaszadegan, Ali Mahmoudi, Sajjad Shafaeibajestan, Ehsan Saburi, Jalil Tavakol-Afshari, Mehdi Hassani, Faezeh Jamali, Shahram Salari, Amir Reza Boroumand, Hamid reza Rahimi Stem Cell Research and Therapy, 2025 Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by the selective loss of motor neurons (MNs), leading to progressive muscle weakness, atrophy, and ultimately paralysis. This review provides a comprehensive overview of the molecular mechanisms underlying ALS pathogenesis, the genetic mutations associated with both familial and sporadic forms of the disease, and the latest therapeutic strategies aimed at mitigating disease progression. mutations in genes such as C9orf72, SOD1, TARDBP, and FUS have been implicated in ALS, with an intricate interplay of protein misfolding, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation contributing to motor neuron degeneration. While current FDA-approved treatments such as Riluzole and Edaravone offer only modest benefits and do not significantly halt disease progression. Emerging therapies, including gene therapies (e.g., antisense oligonucleotides (ASOs) and CRISPR/Cas9, stem cell-based approaches, and neurotrophic factor supplementation, are demonstrating promising results in preclinical and early-phase clinical trials. novel approaches aim to target, modulate, and promote regeneration, renewed hope for future ALS treatments. However, several challenges remain, including effective delivery methods, safety concerns, and the inherent complexity of ALS pathology, ongoing research continues to explore these innovative interventions with the goal of improving clinical outcomes for patients. This review highlights the importance of personalized therapeutic approaches and underscores the necessity of continued innovation in ALS research, with the ultimate goal of developing disease-modifying therapies and, potentially, a cure for this fatal condition.
How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery Mohammad Mahdi Hajihasani, Najmeh Kaffash Farkhad, Ali Mahmoudi, Amirhossein Sahebkar Current Medicinal Chemistry, 2025 The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) is one of the biggest unsolved global problems of the 21<sup>st</sup> century for which there has been no definitive cure yet. Like other respiratory viruses, SARS-COV-2 triggers the host immunity dramatically, causing dysfunction in the immune system, both innate and adaptive, which is a common feature of COVID-19 patients. Evidence shows that in the early stages of COVID-19, the immune system is suppressed while it is overactive in severe patients characterized by excessive and prolonged inflammatory responses called "Cytokine Storm". There are many elements in the immune system that undergo alterations as the disease progresses. Some significant changes in the innate immune system following infection with SARS-COV-2 include delayed or inhibited interferon type 1 production by the infected cells leading to elevated virus replication, excessive recruitment of activated monocytes and macrophages, decrease in eosinophil population (eosinopenia), consequent decrease in CD<sup>8+</sup>T lymphocyte proliferation, natural killer (NK) cell dysfunction, and increase in neutrophil infiltration (neutrophilia) and neutrophil extracellular trap (NET) formation. Moreover, hallmark alterations in the adaptive immune system in this process cause an overall decrease in the T lymphocyte number (lymphopenia) and changes in the activity of some lymphocyte subsets and a number of B cells. This review delves into the mentioned changes in the immune system following SARS-COV-2 infection and the implications thereof to guide the development of immunotherapies for patients with COVID-19.
Statins as a Potential Treatment for Non-alcoholic Fatty Liver Disease: Target Deconvolution using Protein-protein Interaction Network Analysis Ali Mahmoudi, Alexandra E. Butler, Alexander N. Orekhov, Tannaz Jamialahmadi, Amirhossein Sahebkar Current Medicinal Chemistry, 2025 Background: The hallmark of non-alcoholic fatty liver disease (NAFLD) is aberrant buildup of triglycerides (TGs) in hepatocytes. Many genes promote NAFLD development. Using bioinformatics tools, we investigated the possible effect of statins on genes involved in NAFLD progression Methods: Protein interactions of statins and NAFLD were searched in gene-drug and gene-disease databases. A Protein-Protein interaction (PPI) network was constructed to find hub genes and Molecular Complex Detection (MCODE) of NAFLD-related genes. Shared protein targets between protein targets of statins and NAFLD-associated genes were identified. Next, targets of each statin were assayed with all modular clusters in the MCODEs related to NAFLD. Biological process and pathway enrichment analysis for shared proteins was performed. Results: Screening protein targets for conventional statins and curated NAFLD-related genes identified 343 protein targets and 70 genes, respectively. A Venn diagram of NAFLD-related genes and protein targets of statins showed 24 shared proteins. The biological pathways on KEGG enrichment associated with the 24 shared protein sets were evaluated and included cytokine-cytokine receptor interaction, adipocytokine, PPAR, TNF and AMPK signaling pathways. Gene Ontology analysis showed major involvement in lipid metabolic process regulation and inflammatory response. PPI network analysis of 70 protein targets indicated 13 hub genes (PPARA, IL4, CAT, LEP, SREBF1, PRKCA, CYP2E1, NFE2L2, PTEN, NR1H4, ADIPOQ, GSTP1 and TGFB1). Comparing all seven statins with the three MCODE clusterings and 13 hub genes revealed that simvastatin as the most associated statin with NAFLD. Conclusions: Simvastatin has the most impact on NAFLD-related genes versus other statins.
Effect of diabetes on efferocytosis process Ali Mahmoudi, Ali Ahmadizad firouzjaei, Fatemeh darijani, Jamshid Gholizadeh Navashenaq, Eskandar Taghizadeh, Majid Darroudi, Seyed Mohammad Gheibihayat Molecular Biology Reports, 2022
Pleiotropic Effects of Statins: Focus on Endothelial Function, Plaque Stability and Thrombosis (Part II) A Mahmoudi, N Katsiki, M Vrablik, A Sahebkar Current Atherosclerosis Reports 28 (1), 16 , 2026 2026
Pleiotropic effects of statins: focus on Inflammation, oxidative stress and Immunomodulation (Part I) A Mahmoudi, N Katsiki, M Vrablik, A Sahebkar Current Atherosclerosis Reports 28 (1), 8 , 2026 2026 Citations: 3
Uncovering molecular signatures and pathogenic pathways in myotonic dystrophy type 1 through bioinformatic analysis A Mahmoudi, S Karav, P Kesharwani, A Sahebkar Human Gene, 201530 , 2026 2026
Interleukin-1β biosensors: Emerging analytical approaches for precision diagnostics ZJ Bahaabadi, A Mahmoudi, S Karav, P Kesharwani, A Sahebkar Microchemical Journal, 116704 , 2025 2025
Exploring critical hub genes and potential drug candidates for PCOS: A systems biology approach AA Firouzjaei, A Mahmoudi, N Elizova, P Kesharwani, A Sahebkar Reproductive Biology 25 (4), 101078 , 2025 2025
Cutting-edge treatments in amyotrophic lateral sclerosis: the role of molecular pathogenesis in targeted therapies R Raoufinia, G Alyari, AT Nia, MR Abbaszadegan, A Mahmoudi, ... Stem Cell Research & Therapy , 2025 2025 Citations: 1
Investigation of aldose reductase inhibitors: Implications for therapeutic targets in diabetic retinopathy S Ahmad, HAAA Omaima, A Mahmoudi, U Shahab, S Rehman, ... Journal of Molecular Structure 1336, 142004 , 2025 2025
Direct hybridization and bioinformatics analysis of circulating microRNAs in patients with Alzheimer’s disease under intravenous trehalose treatment S Radbakhsh, DM Abrego-Guandique, T Bacchetti, SH Aghaee-Bakhtiari, ... Brain Research 1857, 149607 , 2025 2025 Citations: 10
How does the Immunological System Change during the SARS-COV-2 Attack? A Clue for the New Immunotherapy Discovery MM Hajihasani, NK Farkhad, A Mahmoudi, A Sahebkar Current Medicinal Chemistry 32 (8), 1575-1588 , 2025 2025 Citations: 1
UNCOVERING KEY GENES IN ATHEROSCLEROSIS THROUGH PROTEIN-PROTEIN INTERACTION NETWORK ANALYSIS A Mahmoudi, T Jamialahmadi, A Sahebkar Atherosclerosis 399, 118740 , 2024 2024 Citations: 1
COMPUTATIONAL IDENTIFICATION OF SMALL MOLECULES FOR MODULATING ATHEROSCLEROSIS AND NAFLD A Sahebkar, M JAVID-NADERI, A Mahmoudi, T Jamialahmadi Atherosclerosis 399, 118739 , 2024 2024
IMPACT OF CALEBIN-A ON KEY DIABETES-ASSOCIATED GENES A Mahmoudi, T Jamialahmadi, A Sahebkar Atherosclerosis 399, 118741 , 2024 2024
Stem Cell Therapy as a Potential Treatment of Non-Alcoholic Steatohepatitis-Related End-Stage Liver Disease: A Narrative Review A Mahmoudi, P Meidany, W Almahmeed, T Jamialahmadi, A Sahebkar Current Stem Cell Reports 10 (4), 85-107 , 2024 2024 Citations: 1
MicroRNA delivery by arginine-rich cell-penetrating peptides: An investigation on expression and the cellular uptake mechanisms A Mahmoudi, A Jalili, SH Aghaee-Bakhtiari, RK Oskuee, A Mostafapour, ... Colloids and Surfaces A: Physicochemical and Engineering Aspects 700, 134749 , 2024 2024 Citations: 2
Bioinformatic analysis of the molecular targets of curcumin in colorectal cancer A Mahmoudi, T Jamialahmadi, P Kesharwani, A Sahebkar Pathology-Research and Practice 262, 155533 , 2024 2024 Citations: 14
Exploration of the key genes involved in non-alcoholic fatty liver disease and possible microRNA therapeutic targets A Mahmoudi, A Jalili, AE Butler, SH Aghaee-Bakhtiari, T Jamialahmadi, ... Journal of Clinical and Experimental Hepatology 14 (4), 101365 , 2024 2024 Citations: 4
Trehalose effect in patients with Alzheimer's disease: focus on circulating microRNAs assessed by direct hybridization DM Guandique, S Radbakhsh, T Bacchetti, SH Aghaee-Bakhtiari, ... FEBS OPEN BIO 14, 22-22 , 2024 2024
Effect of Calebin-A on critical genes related to NAFLD: a protein-protein interaction network and molecular docking study A Mahmoudi, MM Hajihasani, M Majeed, T Jamialahmadi, A Sahebkar Current Genomics 25 (2), 120-139 , 2024 2024 Citations: 10
Identification and analysis of the molecular targets of statins in colorectal cancer AA Firouzjaei, A Mahmoudi, W Almahmeed, Y Teng, P Kesharwani, ... Pathology-Research and Practice 256, 155258 , 2024 2024 Citations: 4
Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease A Mahmoudi, A Jalili, SH Aghaee-Bakhtiari, RK Oskuee, AE Butler, ... Journal of Diabetes and its Complications 38 (4), 108722 , 2024 2024 Citations: 3
MOST CITED SCHOLAR PUBLICATIONS
Recent advances in nanogold as a promising nanocarrier for curcumin delivery A Mahmoudi, P Kesharwani, M Majeed, Y Teng, A Sahebkar Colloids and Surfaces B: Biointerfaces 215, 112481 , 2022 2022 Citations: 69
The role of exosomal miRNA in nonalcoholic fatty liver disease A Mahmoudi, AE Butler, T Jamialahmadi, A Sahebkar Journal of Cellular Physiology , 2022 2022 Citations: 67
Impact of fenofibrate on NAFLD/NASH: A genetic perspective A Mahmoudi, T Jamialahmadi, TP Johnston, A Sahebkar Drug discovery today 27 (8), 2363-2372 , 2022 2022 Citations: 50
Liver Protective Effect of Fenofibrate in NASH/NAFLD Animal Models A Mahmoudi, SA Moallem, TP Johnston, A Sahebkar PPAR Research 2022 , 2022 2022 Citations: 39
Therapeutic role of curcumin in diabetes: an analysis based on bioinformatic findings A Mahmoudi, SL Atkin, NG Nikiforov, A Sahebkar Nutrients 14 (15), 3244 , 2022 2022 Citations: 38
How similar are human mesenchymal stem cells derived from different origins? A review of comparative studies NK Farkhad, A Mahmoudi, E Mahdipour Current stem cell research & therapy 16 (8), 980-993 , 2021 2021 Citations: 38
Recent advances of nanotechnology in the treatment and diagnosis of polycystic ovary syndrome MJ Javid-Naderi, A Mahmoudi, P Kesharwani, T Jamialahmadi, ... Journal of Drug Delivery Science and Technology 79, 104014 , 2023 2023 Citations: 35
Investigation of the effect of curcumin on protein targets in NAFLD using bioinformatic analysis A Mahmoudi, AE Butler, M Majeed, M Banach, A Sahebkar Nutrients 14 (7), 1331 , 2022 2022 Citations: 28
Dysregulated balance in Th17/Treg axis of Pristane-induced lupus mouse model, are mesenchymal stem cells therapeutic? A Hoseinzadeh, Z Rezaieyazdi, M Mahmoudi, JT Afshari, FL Arab, ... International immunopharmacology 117, 109699 , 2023 2023 Citations: 26
Construction of a sensitive and specific lead biosensor using a genetically engineered bacterial system with a luciferase gene reporter controlled by pbr and cadA promoters E Nourmohammadi, S Hosseinkhani, R Nedaeinia, H Khoshdel-Sarkarizi, ... BioMedical Engineering OnLine 19 (1), 79 , 2020 2020 Citations: 25
Harnessing aptamers against COVID-19: A therapeutic strategy A Mahmoudi, SH Alavizadeh, SA Hosseini, P Meidany, M Doagooyan, ... Drug Discovery Today 28 (8), 103663 , 2023 2023 Citations: 21
Effect of curcumin on attenuation of liver cirrhosis via genes/proteins and pathways: A system pharmacology study A Mahmoudi, SL Atkin, T Jamialahmadi, M Banach, A Sahebkar Nutrients 14 (20), 4344 , 2022 2022 Citations: 21
Effect of diabetes on efferocytosis process A Mahmoudi, A Ahmadizad Firouzjaei, JG Navashenaq, E Taghizadeh, ... Molecular Biology Reports, 1-15 , 2022 2022 Citations: 21
Target deconvolution of fenofibrate in nonalcoholic fatty liver disease using bioinformatics analysis A Mahmoudi, AE Butler, T Jamialahmadi, A Sahebkar BioMed research international 2021 (1), 3654660 , 2021 2021 Citations: 21
Application of nanotechnology in air purifiers as a viable approach to protect against Corona virus A Mahmoudi, SB Tavakoly Sany, M Ahari Salmasi, A Bakhshi, A Bustan, ... IET nanobiotechnology 17 (4), 289-301 , 2023 2023 Citations: 15
Bioinformatic analysis of the molecular targets of curcumin in colorectal cancer A Mahmoudi, T Jamialahmadi, P Kesharwani, A Sahebkar Pathology-Research and Practice 262, 155533 , 2024 2024 Citations: 14
Role of statins in regulating molecular pathways following traumatic brain injury: A system pharmacology study A Mahmoudi, S Heydari, YV Markina, GE Barreto, A Sahebkar Biomedicine & Pharmacotherapy 153, 113304 , 2022 2022 Citations: 14
Regenerative therapy by using mesenchymal stem cells-derived exosomes in COVID-19 treatment. The potential role and underlying mechanisms NK Farkhad, A Mahmoudi, E Mahdipour Regenerative Therapy 20, 61-71 , 2022 2022 Citations: 14
Efficient genetic transformation of sour orange, Citrus aurantium L. using Agrobacterium tumefaciens containing the coat protein gene of Citrus tristeza virus I Ghaderi, MM Sohani, A Mahmoudi Plant Gene 14, 7-11 , 2018 2018 Citations: 13
siRNA-mediated gene silencing for non-alcoholic fatty liver disease: a comprehensive review of molecular targets A Mahmoudi, M Rostami, MM Hajihasani, VN Sukhorukov, P Kesharwani, ... European Polymer Journal 208, 112866 , 2024 2024 Citations: 11