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Current Chinese Science


ISSN (Print): 2210-2981
ISSN (Online): 2210-2914

Research Article Section: Pharmacology

Exploring the Molecular Mechanisms of Acorus tatarinowii and Ginseng in the Treatment of Autism Spectrum Disorder Based on Network Pharmacology and Molecular Docking

Author(s): Weijun Chen, Yan Wu, Yuan Hu, Liuyan Zhu, Lingling Wu, Guannan Bai* and Chaochun Zou*

Volume 4, Issue 2, 2024

Published on: 05 January, 2024

Page: [145 - 157] Pages: 13

DOI: 10.2174/0122102981280184231214092958


Background: Acorus tatarinowii and Ginseng (AT-G) are traditional Chinese herbal medicines extensively utilized in neurological disorders treatment. However, due to the complex components of AT-G and the pathological mechanism of ASD, the mechanisms involved in the treatment of ASD with AT-G remain elusive.

Objectives: We explored AT-G potential mechanisms in ASD treatment.

Methods: We used the network pharmacology approach to evaluate the beneficial effects of AT-G for ASD, including obtaining the active components of AT-G by the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform, detecting the potential targets genes associated with ASD of Genecards and DisGenet databases, network analysis, and virtual docking.

Results: A total of 26 AT-G components, 130 AT-G targets, and 806 ASD-related genes were identified using the bioinformatics analysis tool, including TCMSP, Genecards, and DisGenet. In the intersection of potential pharmacodynamic targets of AT-G and genes associated with ASD, we identified 41 potential common targets. Then, GO enrichment analysis revealed that the common targets were mainly associated with biological processes (i.e., positive regulation of nitric oxide biosynthetic process, response to xenobiotic stimulus), cellular components (i.e., the presynaptic membrane and postsynaptic membrane), and molecular functions (i.e., RNA polymerase II transcription factor activity, identical protein binding). KEGG pathway analysis found that the common targets were enriched in chemical carcinogenesis - receptor activation, fluid shear stress and atherosclerosis, lipid and atherosclerosis, and IL-17 signaling pathways. In addition, 10 core targets were screened from the PPI network (e.g., TNF, AKT1, PTGS2, IL1B, MMP9, PPARG, IFNG, NOS2, TGFB1, and CASP1). Molecular docking revealed that the common component kaempferol has a high affinity for the four primary disease targets.

Conclusion: Our results facilitated the in-depth development of AT-G and their individual components and provided a reference for clinical practice.

Keywords: Acorus tatarinowii, Ginseng, autism spectrum disorder, network pharmacology, molecular docking, molecular mechanism.

Graphical Abstract
Lord, C.; Elsabbagh, M.; Baird, G.; Veenstra-Vanderweele, J. Autism spectrum disorder. Lancet, 2018, 392(10146), 508-520.
[] [PMID: 30078460]
Zhou, H.; Xu, X.; Yan, W.; Zou, X.; Wu, L.; Luo, X.; Li, T.; Huang, Y.; Guan, H.; Chen, X.; Mao, M.; Xia, K.; Zhang, L.; Li, E.; Ge, X.; Zhang, L.; Li, C.; Zhang, X.; Zhou, Y.; Ding, D.; Shih, A.; Fombonne, E.; Zheng, Y.; Han, J.; Sun, Z.; Jiang, Y.; Wang, Y. Prevalence of Autism Spectrum Disorder in China: A nationwide multi-center population-based study among children aged 6 to 12 years. Neurosci. Bull., 2020, 36(9), 961-971.
[] [PMID: 32607739]
Lavelle, T.A.; Weinstein, M.C.; Newhouse, J.P.; Munir, K.; Kuhlthau, K.A.; Prosser, L.A. Economic burden of childhood autism spectrum disorders. Pediatrics, 2014, 133(3), e520-e529.
[] [PMID: 24515505]
Dong, Y.; Zhao, K.; Qin, X.; Du, G.; Gao, L. The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases. Ageing Res. Rev., 2023, 92, 102092.
[] [PMID: 37839757]
Gong, L.; Yin, J.; Zhang, Y.; Huang, R.; Lou, Y.; Jiang, H.; Sun, L.; Jia, J.; Zeng, X. Neuroprotective Mechanisms of ginsenoside Rb1 in central nervous system diseases. Front. Pharmacol., 2022, 13, 914352.
[] [PMID: 35721176]
Zhang, Y.; Long, Y.; Yu, S.; Li, D.; Yang, M.; Guan, Y.; Zhang, D.; Wan, J.; Liu, S.; Shi, A.; Li, N.; Peng, W. Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder. Pharmacol. Res., 2021, 164, 105376.
[] [PMID: 33316383]
Zhang, F.H.; Wang, Z.M.; Liu, Y.T.; Huang, J.S.; Liang, S.; Wu, H.H.; Xu, Y.T. Bioactivities of serotonin transporter mediate antidepressant effects of Acorus tatarinowii Schott. J. Ethnopharmacol., 2019, 241, 111967.
[] [PMID: 31128148]
Zhong, J.; Qiu, X.; Yu, Q.; Chen, H.; Yan, C. A novel polysaccharide from Acorus tatarinowii protects against LPS-induced neuroinflammation and neurotoxicity by inhibiting TLR4-mediated MyD88/NF-κB and PI3K/Akt signaling pathways. Int. J. Biol. Macromol., 2020, 163, 464-475.
[] [PMID: 32621930]
Hou, W.; Wang, Y.; Zheng, P.; Cui, R. Effects of Ginseng on neurological disorders. Front. Cell. Neurosci., 2020, 14, 55.
[] [PMID: 32265659]
Wang, N.; Wang, X.; He, M.; Zheng, W.; Qi, D.; Zhang, Y.; Han, C. Ginseng polysaccharides: A potential neuroprotective agent. J. Ginseng Res., 2021, 45(2), 211-217.
[] [PMID: 33841001]
Zhu, Y.; Wang, Z.; Yu, S.; Zhao, C.; Xu, B.; Liu, R.; Xu, L.; Guo, Y. Neuroprotective Effect of Ginseng fibrous root enzymatic hydrolysate against oxidative stress. Molecules, 2022, 27(22), 7824.
[] [PMID: 36431931]
Zarneshan, S.N.; Fakhri, S.; Khan, H. Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach. Pharmacol. Res., 2022, 177, 106099.
[] [PMID: 35092819]
Ji, Y.J.; Kim, H.D.; Lee, E.S.; Jang, G.Y.; Seong, H.A. Heat treatment enhances the neuroprotective effects of crude ginseng saponin by increasing minor ginsenosides. Int. J. Mol. Sci., 2023, 24(8), 7223.
[] [PMID: 37108384]
Yang, Z.; Zhang, Q.; Yu, L.; Zhu, J.; Cao, Y.; Gao, X. The signaling pathways and targets of traditional Chinese medicine and natural medicine in triple-negative breast cancer. J. Ethnopharmacol., 2021, 264, 113249.
[] [PMID: 32810619]
Ding, M.R.; Qu, Y.J.; Hu, B.; An, H.M. Signal pathways in the treatment of Alzheimer’s disease with traditional Chinese medicine. Biomed. Pharmacother., 2022, 152, 113208.
Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional chinese medicine: Review and Assessment. Front. Pharmacol., 2019, 10, 123.
[] [PMID: 30846939]
Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690.
[] [PMID: 18936753]
Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13.
[] [PMID: 24735618]
Stelzer, G; Rosen, N; Plaschkes, I; Zimmerman, S; Twik, M; Fishilevich, S The GeneCards suite: From gene data mining to disease genome sequence analyses. Curr Protoc Bioinformatics, 2016, 54, 1 30 31-31 30 33.
Piñero, J.; Saüch, J.; Sanz, F.; Furlong, L.I. The DisGeNET cytoscape app: Exploring and visualizing disease genomics data. Comput. Struct. Biotechnol. J., 2021, 19, 2960-2967.
[] [PMID: 34136095]
Sherman, B.T.; Hao, M.; Qiu, J.; Jiao, X.; Baseler, M.W.; Lane, H.C.; Imamichi, T.; Chang, W. DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res., 2022, 50(W1), W216-W221.
[] [PMID: 35325185]
Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612.
[] [PMID: 33237311]
Eberhardt, J.; Santos-Martins, D.; Tillack, A.F.; Forli, S. AutoDock vina 1.2.0: New docking methods, expanded force field, and python bindings. J. Chem. Inf. Model., 2021, 61(8), 3891-3898.
[] [PMID: 34278794]
Hodges, H.; Fealko, C.; Soares, N. Autism spectrum disorder: Definition, epidemiology, causes, and clinical evaluation. Transl. Pediatr., 2020, 9(S1)(Suppl. 1), S55-S65.
[] [PMID: 32206584]
Kodak, T.; Bergmann, S. Autism spectrum disorder. Pediatr. Clin. North Am., 2020, 67(3), 525-535.
[] [PMID: 32443991]
Sharma, S.R.; Gonda, X.; Tarazi, F.I. Autism spectrum disorder: Classification, diagnosis and therapy. Pharmacol. Ther., 2018, 190, 91-104.
[] [PMID: 29763648]
Lam, K.Y.C.; Chen, J.; Lam, C.T.W.; Wu, Q.; Yao, P.; Dong, T.T.X.; Lin, H.; Tsim, K.W.K. Asarone from acori tatarinowii rhizoma potentiates the nerve growth factor-induced neuronal differentiation in cultured PC12 cells: A signaling mediated by protein kinase A. PLoS One, 2016, 11(9), e0163337.
[] [PMID: 27685847]
Mao, J.; Huang, S.; Liu, S.; Feng, X.L.; Yu, M.; Liu, J.; Sun, Y.E.; Chen, G.; Yu, Y.; Zhao, J.; Pei, G. A herbal medicine for Alzheimer’s disease and its active constituents promote neural progenitor proliferation. Aging Cell, 2015, 14(5), 784-796.
[] [PMID: 26010330]
Kim, K.W.; Lee, Y.S.; Choi, B.R.; Yoon, D.; Lee, D.Y. Anti-neuroinflammatory effect of the ethanolic extract of black ginseng through TLR4-MyD88-regulated inhibition of NF-κB and MAPK signaling pathways in LPS-induced BV2 microglial cells. Int. J. Mol. Sci., 2023, 24(20), 15320.
[] [PMID: 37894998]
Lee, M.J.; Choi, J.H.; Kwon, T.W.; Jo, H.S.; Ha, Y.; Nah, S.Y.; Cho, I.H. Korean Red Ginseng extract ameliorates demyelination by inhibiting infiltration and activation of immune cells in cuprizone-administrated mice. J. Ginseng Res., 2023, 47(5), 672-680.
[] [PMID: 37720568]
Xu, Z.; Zhou, X.; Hong, X.; Wang, S.; Wei, J.; Huang, J.; Ji, L.; Yang, Y.; Efferth, T.; Hong, C.; Li, C. Essential oil of Acorus tatarinowii Schott inhibits neuroinflammation by suppressing NLRP3 inflammasome activation in 3×Tg-AD transgenic mice. Phytomedicine, 2023, 112, 154695.
[] [PMID: 36774844]
Gao, X.; Li, R.; Luo, L.; Liao, C.; Yang, H.; Mao, S. Alpha-asarone ameliorates neurological dysfunction of subarachnoid hemorrhagic rats in both acute and recovery phases via regulating the CaMKII-dependent pathways. Transl. Stroke Res., 2023, 1-19.
[] [PMID: 36781743]
Wang, N.; Wang, H.; Pan, Q.; Kang, J.; Liang, Z.; Zhang, R. The combination of β-asarone and icariin inhibits amyloid-β and reverses cognitive deficits by promoting mitophagy in models of alzheimer’s disease. Oxid. Med. Cell. Longev., 2021, 2021, 1-20.
[] [PMID: 34887998]
Zhao, X.; Liang, L.; Xu, R.; Cheng, P.; Jia, P.; Bai, Y.; Zhang, Y.; Zhao, X.; Zheng, X.; Xiao, C. Revealing the antiepileptic effect of α-asaronol on pentylenetetrazole-induced seizure rats using NMR-based metabolomics. ACS Omega, 2022, 7(7), 6322-6334.
[] [PMID: 35224394]
Huang, X.; Li, N.; Pu, Y.; Zhang, T.; Wang, B. Neuroprotective effects of ginseng phytochemicals: Recent perspectives. Molecules, 2019, 24(16), 2939.
[] [PMID: 31416121]
Wang, W.; Wang, L.; Wang, L.; Li, Y.; Lan, T.; Wang, C.; Chen, X.; Chen, S.; Yu, S. Ginsenoside-Rg1 synergized with voluntary running exercise protects against glial activation and dysregulation of neuronal plasticity in depression. Food Funct., 2023, 14(15), 7222-7239.
[] [PMID: 37464840]
Tan, X.; Gu, J.; Zhao, B.; Wang, S.; Yuan, J.; Wang, C.; Chen, J.; Liu, J.; Feng, L.; Jia, X. Ginseng improves cognitive deficit via the RAGE/NF-κB pathway in advanced glycation end product-induced rats. J. Ginseng Res., 2015, 39(2), 116-124.
[] [PMID: 26045684]
Li, H.; Kang, T.; Qi, B.; Kong, L.; Jiao, Y.; Cao, Y.; Zhang, J.; Yang, J. Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D -galactose/AlCl3 inducing rats model of Alzheimer’s disease. J. Ethnopharmacol., 2016, 179, 162-169.
[] [PMID: 26721223]
Wu, J.; Yang, Y.; Wan, Y.; Xia, J.; Xu, J.F.; Zhang, L.; Liu, D.; Chen, L.; Tang, F.; Ao, H.; Peng, C. New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer’s disease. Biomed. Pharmacother., 2022, 152, 113207.
[] [PMID: 35667236]
Oh, J.; Kim, J.S. Compound K derived from ginseng: Neuroprotection and cognitive improvement. Food Funct., 2016, 7(11), 4506-4515.
[] [PMID: 27801453]
Gao, X.C.; Zhang, N.X.; Shen, J.M.; Lv, J.W.; Zhang, K.Y.; Sun, Y.; Li, H.; Wang, Y.L.; Cheng, D.D.; Zhao, M.Y.; Zhang, H.; Li, C.N.; Sun, J.M. Screening of the active compounds against neural oxidative damage from ginseng phloem using UPLC-Q-Exactive-MS/MS coupled with the content-effect weighted method. Molecules, 2022, 27(24), 9061.
[] [PMID: 36558193]
Jakaria, M.; Kim, J.; Karthivashan, G.; Park, S.Y.; Ganesan, P.; Choi, D.K. Emerging signals modulating potential of Ginseng and its active compounds focusing on neurodegenerative diseases. J. Ginseng Res., 2019, 43(2), 163-171.
[] [PMID: 30976157]
Imran, M.; Salehi, B.; Sharifi-Rad, J.; Aslam Gondal, T.; Saeed, F.; Imran, A.; Shahbaz, M.; Tsouh Fokou, P.V.; Umair Arshad, M.; Khan, H.; Guerreiro, S.G.; Martins, N.; Estevinho, L.M. Kaempferol: A key emphasis to its anticancer potential. Molecules, 2019, 24(12), 2277.
[] [PMID: 31248102]
Feng, Z.; Wang, C.; Jin, Y.; Meng, Q.; Wu, J.; Sun, H.; Sun, H. Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway. Pharm. Biol., 2021, 59(1), 1104-1114.
[] [PMID: 34403325]
Dabeek, W.M.; Marra, M.V. Dietary quercetin and kaempferol: Bioavailability and potential cardiovascular-related bioactivity in humans. Nutrients, 2019, 11(10), 2288.
[] [PMID: 31557798]
Chen, Y.; Ma, K.; Si, H.; Duan, Y.; Zhai, H. Network pharmacology integrated molecular docking to reveal the autism and mechanism of baohewan heshiwei wen dan tang. Curr. Pharm. Des., 2022, 28(39), 3231-3241.
[] [PMID: 36165527]
Chang, S.; Li, X.; Zheng, Y.; Shi, H.; Zhang, D.; Jing, B.; Chen, Z.; Qian, G.; Zhao, G. Kaempferol exerts a neuroprotective effect to reduce neuropathic pain through TLR4/NF‐ĸB signaling pathway. Phytother. Res., 2022, 36(4), 1678-1691.
[] [PMID: 35234314]
Cheng, K.; Chen, Y.; Yue, C.; Zhang, S.; Pei, Y.P.; Cheng, G.; Liu, D.; Xu, L.; Dong, H.; Zeng, Y. Calsyntenin-1 negatively regulates ICAM5 accumulation in postsynaptic membrane and influences dendritic spine maturation in a mouse model of fragile X syndrome. Front. Neurosci., 2019, 13, 1098.
[] [PMID: 31680833]
Babatz, T.D.; Kumar, R.A.; Sudi, J.; Dobyns, W.B.; Christian, S.L. Copy number and sequence variants implicate APBA2 as an autism candidate gene. Autism Res., 2009, 2(6), 359-364.
[] [PMID: 20029827]
Traglia, M.; Croen, L.A.; Lyall, K.; Windham, G.C.; Kharrazi, M.; DeLorenze, G.N.; Torres, A.R.; Weiss, L.A. Independent maternal and fetal genetic effects on midgestational circulating levels of environmental pollutants. G3, 2017, 7(4), 1287-1299.
[] [PMID: 28235828]
Mehta, R.; Kuhad, A.; Bhandari, R. Nitric oxide pathway as a plausible therapeutic target in autism spectrum disorders. Expert Opin. Ther. Targets, 2022, 26(7), 659-679.
[] [PMID: 35811505]
Mehta, R.; Bhandari, R.; Kuhad, A. Effects of catechin on a rodent model of autism spectrum disorder: Implications for the role of nitric oxide in neuroinflammatory pathway. Psychopharmacology, 2021, 238(11), 3249-3271.
[] [PMID: 34448020]
Santos, J.X.; Rasga, C.; Marques, A.R.; Martiniano, H.; Asif, M.; Vilela, J.; Oliveira, G.; Sousa, L.; Nunes, A.; Vicente, A.M. A role for gene-environment interactions in autism spectrum disorder is supported by variants in genes regulating the effects of exposure to xenobiotics. Front. Neurosci., 2022, 16, 862315.
[] [PMID: 35663546]
Kong, Y.; Zhou, W.; Sun, Z. Nuclear receptor corepressors in intellectual disability and autism. Mol. Psychiatry, 2020, 25(10), 2220-2236.
[] [PMID: 32034290]
Tripathi, M.K.; Kartawy, M.; Ginzburg, S.; Amal, H. Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer’s disease-associated mutations. Transl. Psychiatry, 2022, 12(1), 127.
[] [PMID: 35351881]
Wang, J.; Fröhlich, H.; Torres, F.B.; Silva, R.L.; Poschet, G.; Agarwal, A.; Rappold, G.A. Mitochondrial dysfunction and oxidative stress contribute to cognitive and motor impairment in FOXP1 syndrome. Proc. Natl. Acad. Sci., 2022, 119(8), e2112852119.
[] [PMID: 35165191]
Singh, K.; Connors, S.L.; Macklin, E.A.; Smith, K.D.; Fahey, J.W.; Talalay, P.; Zimmerman, A.W. Sulforaphane treatment of autism spectrum disorder (ASD). Proc. Natl. Acad. Sci., 2014, 111(43), 15550-15555.
[] [PMID: 25313065]
Thawley, A.J.; Veneziani, L.P.; Rabelo-da-Ponte, F.D.; Riederer, I.; Mendes-da-Cruz, D.A.; Bambini-Junior, V. Aberrant IL-17 levels in rodent models of autism spectrum disorder: A systematic review. Front. Immunol., 2022, 13, 874064.
[] [PMID: 35757754]
Nadeem, A.; Ahmad, S.F.; Attia, S.M.; Bakheet, S.A.; Al-Harbi, N.O.; AL-Ayadhi, L.Y. Activation of IL-17 receptor leads to increased oxidative inflammation in peripheral monocytes of autistic children. Brain Behav. Immun., 2018, 67, 335-344.
[] [PMID: 28935156]
Ahmad, S.F.; Ansari, M.A.; Nadeem, A.; Bakheet, S.A.; Alshammari, M.A.; Attia, S.M. Protection by tyrosine kinase inhibitor, tyrphostin AG126, through the suppression of IL-17A, RORγt, and T-bet signaling, in the BTBR mouse model of autism. Brain Res. Bull., 2018, 142, 328-337.
[] [PMID: 30172736]
Gevezova, M.; Sarafian, V.; Anderson, G.; Maes, M. Inflammation and mitochondrial dysfunction in autism spectrum disorder. CNS Neurol. Disord. Drug Targets, 2020, 19(5), 320-333.
[] [PMID: 32600237]
Theoharides, T.C.; Tsilioni, I.; Patel, A.B.; Doyle, R. Atopic diseases and inflammation of the brain in the pathogenesis of autism spectrum disorders. Transl. Psychiatry, 2016, 6(6), e844.
[] [PMID: 27351598]
Luhach, K.; Kulkarni, G.T.; Singh, V.P.; Sharma, B. Attenuation of neurobehavioural abnormalities by papaverine in prenatal valproic acid rat model of ASD. Eur. J. Pharmacol., 2021, 890, 173663.
[] [PMID: 33127361]
Zhang, J.; Zhang, J.X.; Zhang, Q.L. PI3K/AKT/mTOR-mediated autophagy in the development of autism spectrum disorder. Brain Res. Bull., 2016, 125, 152-158.
[] [PMID: 27320472]
Thomas, S.D.; Jha, N.K.; Ojha, S.; Sadek, B. mTOR signaling disruption and its association with the development of autism spectrum disorder. Molecules, 2023, 28(4), 1889.
[] [PMID: 36838876]
Xing, X.; Zhang, J.; Wu, K.; Cao, B.; Li, X.; Jiang, F.; Hu, Z.; Xia, K.; Li, J.D. Suppression of Akt-mTOR pathway rescued the social behavior in Cntnap2-deficient mice. Sci. Rep., 2019, 9(1), 3041.
[] [PMID: 30816216]
Li, H.; Zhang, Q.; Wan, R.; Zhou, L.; Xu, X.; Xu, C.; Yu, Y.; Xu, Y.; Xiang, Y.; Tang, S. PLPPR4 haploinsufficiency causes neurodevelopmental disorders by disrupting synaptic plasticity via MTOR signalling. J. Cell. Mol. Med., 2023, 27(21), 3286-3295.
[] [PMID: 37550884]
El-Ansary, A.; Alhakbany, M.; Aldbass, A.; Qasem, H.; Al-Mazidi, S.; Bhat, R.S.; Al-Ayadhi, L. Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values. Lipids Health Dis., 2021, 20(1), 155.
[] [PMID: 34742290]
Abdallah, M.W.; Pearce, B.D.; Larsen, N.; Greaves-Lord, K.; Nørgaard-Pedersen, B.; Hougaard, D.M.; Mortensen, E.L.; Grove, J. Amniotic fluid MMP-9 and neurotrophins in autism spectrum disorders: An exploratory study. Autism Res., 2012, 5(6), 428-433.
[] [PMID: 23008271]
Pirbhoy, P.S.; Rais, M.; Lovelace, J.W.; Woodard, W.; Razak, K.A.; Binder, D.K.; Ethell, I.M. Acute pharmacological inhibition of matrix metalloproteinase‐9 activity during development restores perineuronal net formation and normalizes auditory processing in Fmr1 KO mice. J. Neurochem., 2020, 155(5), 538-558.
[] [PMID: 32374912]
Abdallah, M.W.; Mortensen, E.L.; Greaves-Lord, K.; Larsen, N.; Bonefeld-Jørgensen, E.C.; Nørgaard-Pedersen, B.; Hougaard, D.M.; Grove, J. Neonatal levels of neurotrophic factors and risk of autism spectrum disorders. Acta Psychiatr. Scand., 2013, 128(1), 61-69.
[] [PMID: 23039165]
Fallah, H.; Sayad, A.; Ranjbaran, F.; Talebian, F.; Ghafouri-Fard, S.; Taheri, M. IFNG/IFNG-AS1 expression level balance: Implications for autism spectrum disorder. Metab. Brain Dis., 2020, 35(2), 327-333.
[] [PMID: 31728886]
Nadeem, A.; Ahmad, S.F.; Attia, S.M.; AL-Ayadhi, L.Y.; Bakheet, S.A.; Al-Harbi, N.O. Oxidative and inflammatory mediators are upregulated in neutrophils of autistic children: Role of IL-17A receptor signaling. Prog. Neuropsychopharmacol. Biol. Psychiatry, 2019, 90, 204-211.
[] [PMID: 30529000]
Liu, L.; Fu, Q.; Ding, H.; Jiang, H.; Zhan, Z.; Lai, Y. Combination of machine learning-based bulk and single-cell genomics reveals necroptosis-related molecular subtypes and immunological features in autism spectrum disorder. Front. Immunol., 2023, 14, 1139420.
[] [PMID: 37168851]
Majerczyk, D.; Ayad, E.G.; Brewton, K.L.; Saing, P.; Hart, P.C. Systemic maternal inflammation promotes ASD via IL-6 and IFN-. Biosci. Rep., 2022, 42(11), BSR20220713.
[] [PMID: 36300375]

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