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2000
Volume 32, Issue 41
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Introduction

Parkinson's disease (PD) is a neurodegenerative disorder associated with a progressive loss of dopaminergic cells and as of now, there is no established definitive treatment available for this condition.

Methods

In this study, the focus was on investigating the impact of SVAK-12, a small molecule that can cross the blood-brain barrier and remain stable without structural changes. The effect of SVAK-12 was investigated on neurotoxicity, model of Parkinson's diseases and .

Results

Through and experiments, as well as molecular docking simulations, it was found that SVAK-12 (375 ng.ml) led to increased cell viability, reduced cellular damage, and decreased production of NO and ROS. Additionally, it boosted levels of important neurotrophic factors like BDNF (130.49%) and GDNF (116.38%), potentially aiding in alleviating motor disability and depression. The study also highlighted SVAK-12's potential as a therapeutic candidate for neurological disorders due to its ability to increase tyrosine hydroxylase expression and dopamine levels (4.84 times). While it did not significantly improve motor symptoms , it did enhance motor asymmetry in the forelimbs and gene expression related to brain regions. Besides, it induced significant BMP-2 gene expression in substantial nigra regions without significant changes in GDNF and Nurr1 gene expression in the striatum expression. The docking of SVAK-12, Levodopa, Amantadine, Biperiden, Selegiline, and Rasagiline to the binding site of GFRα1, sortilin, and TrkB showed that SVAK-12 had greater MolDock score than Selegiline and Amantadine for GFRα1 and greater than amantadine for Sortilin and TrKB.

Conclusion

Overall, the study suggests that SVAK-12's neuro-biocompatibility, ability to reduce free radicals, and enhanced neurotrophic factors make it a promising candidate as a neuroprotective drug.

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References

  1. AarslandD. BatzuL. HallidayG.M. GeurtsenG.J. BallardC. Ray ChaudhuriK. WeintraubD. Parkinson disease-associated cognitive impairment.Nat. Rev. Dis. Primers2021714710.1038/s41572‑021‑00280‑334210995
     [Google Scholar]
  2. SabaeiM. RahimianS. KetabforoushA.H.M.E. RasoolijaziH. ZamaniB. HajiakhoundiF. SoleimaniM. ShahidiG. FaramarziM. Salivary levels of disease-related biomarkers in the early stages of Parkinson's and Alzheimer's disease: A cross-sectional study.IBRO Neurosci Rep.20231428529210.1016/j.ibneur.2023.03.004
     [Google Scholar]
  3. Parkinson disease.2023 Available from: https://www.who.int/news-room/fact-sheets/detail/parkinson-disease
  4. DorseyE.R. ShererT. OkunM.S. BloemB.R. The emerging evidence of the Parkinson pandemic.J. Parkinsons Dis.20188s1S3S810.3233/JPD‑18147430584159
     [Google Scholar]
  5. KouliA. TorsneyK.M. KuanW-L. Parkinson’s disease: Etiology, neuropathology, and pathogenesis.Parkinson’s Disease: Pathogenesis and Clinical Aspects StokerT.B. GreenlandJ.C. Codon Publications201832610.15586/codonpublications.parkinsonsdisease.2018.ch1.
     [Google Scholar]
  6. LindholmP. SaarmaM. Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism.Mol. Psychiatry20222731310132110.1038/s41380‑021‑01394‑634907395
     [Google Scholar]
  7. MaitiP. MannaJ. DunbarG.L. Current understanding of the molecular mechanisms in Parkinson’s disease: Targets for potential treatments.Transl. Neurodegener.2017612810.1186/s40035‑017‑0099‑z29090092
     [Google Scholar]
  8. BarkerR.A. BjörklundA. GashD.M. WhoneA. Van LaarA. KordowerJ.H. BankiewiczK. KieburtzK. SaarmaM. BoomsS. HuttunenH.J. KellsA.P. FiandacaM.S. StoesslA.J. EidelbergD. FederoffH. VoutilainenM.H. DexterD.T. EberlingJ. BrundinP. IsaacsL. MursaleenL. BresolinE. CarrollC. ColesA. FiskeB. MatthewsH. LunguC. WyseR.K. StottS. LangA.E. GDNF and Parkinson’s disease: Where next? A summary from a recent workshop.J. Parkinsons Dis.202010387589110.3233/JPD‑20200432508331
     [Google Scholar]
  9. KramerE.R. LissB. GDNF–Ret signaling in midbrain dopaminergic neurons and its implication for Parkinson disease.FEBS Lett.20155893760377210.1016/j.febslet.2015.11.00626555190
     [Google Scholar]
  10. HamidpourS.K. AmiriM. KetabforoushA.H.M.E. SaeediS. AngajiA. TavakolS.J.M.N. Unraveling dysregulated cell signaling pathways, genetic and epigenetic mysteries of Parkinson's disease.Mol Neurobiol202410.1007/s12035‑024‑04128‑1.
     [Google Scholar]
  11. CortésD. Carballo-MolinaO.A. Castellanos-MontielM.J. VelascoI. The non-survival effects of glial cell line-derived neurotrophic factor on neural cells.Front. Mol. Neurosci.20171025810.3389/fnmol.2017.0025828878618
     [Google Scholar]
  12. MahatoA.K. SidorovaY.A. RET receptor tyrosine kinase: Role in neurodegeneration, obesity, and cancer.Int. J. Mol. Sci.20202119710810.3390/ijms2119710832993133
     [Google Scholar]
  13. KambeyP.A. KanworeK. AyanlajaA.A. NadeemI. DuY. BuberwaW. LiuW. GaoD. Failure of glial cell-line derived neurotrophic factor (GDNF) in clinical trials orchestrated by reduced NR4A2 (NURR1) transcription factor in Parkinson’s disease. A systematic review.Front. Aging Neurosci.20211364558310.3389/fnagi.2021.64558333716718
     [Google Scholar]
  14. ChuY. LeW. KompolitiK. JankovicJ. MufsonE.J. KordowerJ.H. Nurr1 in Parkinson’s disease and related disorders.J. Comp. Neurol.2006494349551410.1002/cne.2082816320253
     [Google Scholar]
  15. HeuckerothR.O. KotzbauerP. CopelandN.G. GilbertD.J. JenkinsN.A. ZimonjicD.B. PopescuN.C. JohnsonE.M.Jr MilbrandtJ. Neurturin, a novel neurotrophic factor, is localized to mouse chromosome 17 and human chromosome 19p13.3.Genomics199744113714010.1006/geno.1997.48469286710
     [Google Scholar]
  16. TenenbaumL. Humbert-ClaudeM. Glial cell line-derived neurotrophic factor gene delivery in Parkinson’s disease: A delicate balance between neuroprotection, trophic effects, and unwanted compensatory mechanisms.Front. Neuroanat.2017112910.3389/fnana.2017.0002928442998
     [Google Scholar]
  17. LeeT.K. YankeeE.L. A review on Parkinson’s disease treatment.Neuroimmunol. Neuroinflamm.2022822210.20517/2347‑8659.2020.58
     [Google Scholar]
  18. AdhikaryR.R. SandbhorP. BanerjeeR. Nanotechnology platforms in Parkinson’s disease.ADMET DMPK20153315518110.5599/admet.3.3.189
     [Google Scholar]
  19. LiQ. KangC. Mechanisms of action for small molecules revealed by structural biology in drug discovery.Int. J. Mol. Sci.20202115526210.3390/ijms2115526232722222
     [Google Scholar]
  20. HanX. SunS. SunY. SongQ. ZhuJ. SongN. ChenM. SunT. XiaM. DingJ. LuM. YaoH. HuG. Small molecule-driven NLRP3 inflammation inhibition via interplay between ubiquitination and autophagy: Implications for Parkinson disease.Autophagy201915111860188110.1080/15548627.2019.159648130966861
     [Google Scholar]
  21. ZhangH. TongR. BaiL. ShiJ. OuyangL. Emerging targets and new small molecule therapies in Parkinson’s disease treatment.Bioorg. Med. Chem.20162471419143010.1016/j.bmc.2016.02.03026935940
     [Google Scholar]
  22. WongE. SangadalaS. BodenS.D. YoshiokaK. HuttonW.C. OliverC. TitusL. A novel low-molecular-weight compound enhances ectopic bone formation and fracture repair.J. Bone Joint Surg. Am.201395545446110.2106/JBJS.L.0027523467869
     [Google Scholar]
  23. KatoS. SangadalaS. TomitaK. TitusL. BodenS.D. A synthetic compound that potentiates bone morphogenetic protein-2-induced transdifferentiation of myoblasts into the osteoblastic phenotype.Mol. Cell. Biochem.20113491-29710610.1007/s11010‑010‑0664‑621110071
     [Google Scholar]
  24. TavakolS. The twofold role of osteogenic small molecules in Parkinson's disease therapeutics: Crosstalk of osteogenesis and neurogenesis.Biomed. Res. Int.20222022381354110.1155/2022/3813541.
     [Google Scholar]
  25. PoormoghadamD. AlmasiA. AshrafizadehM. VishkaeiA.S. RezayatS.M. TavakolS.J.N. The particle size of drug nanocarriers dictates the fate of neurons; critical points in neurological therapeutics.Nanotechnology2020313333510110.1088/1361‑6528/ab8d6b.
     [Google Scholar]
  26. LucianiK.R. FrieJ.A. KhokharJ.Y. An open source automated bar test for measuring catalepsy in rats.eNeuro20207310.1523/ENEURO.0488‑19.202032198157
     [Google Scholar]
  27. MagnoL.A. CollodettiM. Tenza-FerrerH. Romano-SilvaM. Cylinder test to assess sensory-motor function in a mouse model of Parkinson’s disease.Bio Protoc.2019916e3337e333710.21769/BioProtoc.333733654842
     [Google Scholar]
  28. ShiX. BaiH. WangJ. WangJ. HuangL. HeM. ZhengX. DuanZ. ChenD. ZhangJ. ChenX. WangJ. Behavioral assessment of sensory, motor, emotion, and cognition in rodent models of intracerebral hemorrhage.Front. Neurol.20211266751110.3389/fneur.2021.66751134220676
     [Google Scholar]
  29. HuangL. XiaoD. SunH. QuY. SuX. Behavioral tests for evaluating the characteristics of brain diseases in rodent models: Optimal choices for improved outcomes (Review).Mol. Med. Rep.202225518310.3892/mmr.2022.1269935348193
     [Google Scholar]
  30. MiyanishiK. ChoudhuryM.E. WatanabeM. KuboM. NomotoM. YanoH. TanakaJ. Behavioral tests predicting striatal dopamine level in a rat hemi-Parkinson’s disease model.Neurochem. Int.2019122384610.1016/j.neuint.2018.11.00530419255
     [Google Scholar]
  31. ArjmandB. HamidpourS.K. Alavi-MoghadamS. YavariH. ShahbazbadrA. TaviraniM.R. GilanyK. LarijaniB. Molecular docking as a therapeutic approach for targeting cancer stem cell metabolic processes.Front. Pharmacol.20221376855610.3389/fphar.2022.76855635264950
     [Google Scholar]
  32. GumberA. RamaswamyB. ThongchundeeO. Effects of Parkinson’s on employment, cost of care, and quality of life of people with condition and family caregivers in the UK: A systematic literature review.Patient Relat. Outcome Meas.20191032133310.2147/PROM.S16084331695537
     [Google Scholar]
  33. Carvajal-OliverosA. Uriostegui-ArcosM. ZuritaM. Melchy-PerezE.I. Narváez-PadillaV. ReynaudE. The BE (2)-M17 cell line has a better dopaminergic phenotype than the traditionally used for Parkinson´s research SH-SY5Y, which is mostly serotonergic.IBRO Neuroscience Reports20221354355110.1016/j.ibneur.2022.11.00736471713
     [Google Scholar]
  34. CaoY. WangC. ZhangX. XingG. LuK. GuY. HeF. ZhangL. Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation.Sci. Rep.201441496510.1038/srep0496524828823
     [Google Scholar]
  35. Albert-GascóH. Ros-BernalF. Castillo-GómezE. Olucha-BordonauF.E. MAP/ERK signaling in developing cognitive and emotional function and its effect on pathological and neurodegenerative processes.Int. J. Mol. Sci.20202112447110.3390/ijms2112447132586047
     [Google Scholar]
  36. LiuM. ZuoS. GuoX. PengJ. XingY. GuoY. LiC. XingH. The study of overexpression of peroxiredoxin-2 reduces MPP+-induced toxicity in the cell model of Parkinson’s disease.Neurochem. Res.20234872129213710.1007/s11064‑023‑03880‑536808393
     [Google Scholar]
  37. MolinariC. MorsanutoV. RugaS. NotteF. FarghaliM. GallaR. UbertiF. The role of BDNF on aging-modulation markers.Brain Sci.202010528510.3390/brainsci1005028532397504
     [Google Scholar]
  38. XiongZ.K. LangJ. XuG. LiH.Y. ZhangY. WangL. SuY. SunA.J. Excessive levels of nitric oxide in rat model of Parkinson’s disease induced by rotenone.Exp. Ther. Med.20159255355810.3892/etm.2014.209925574233
     [Google Scholar]
  39. DiasV. JunnE. MouradianM.M. The role of oxidative stress in Parkinson’s disease.J. Parkinsons Dis.20133446149110.3233/JPD‑13023024252804
     [Google Scholar]
  40. TristB.G. HareD.J. DoubleK.L. Oxidative stress in the aging substantia nigra and the etiology of Parkinson’s disease.Aging Cell2019186e1303110.1111/acel.1303131432604
     [Google Scholar]
  41. Tapia-GonzálezS. Giráldez-PérezR.M. CuarteroM.I. CasarejosM.J. MenaM.Á. WangX.F. Sánchez-CapeloA. Dopamine and α-synuclein dysfunction in Smad3 null mice.Mol. Neurodegener.2011617210.1186/1750‑1326‑6‑7221995845
     [Google Scholar]
  42. QueZ. ZhouZ. LiuS. ZhengW. LeiB. Dihydroartemisinin inhibits EMT of glioma via gene BASP1 in extrachromosomal DNA.Biochem. Biophys. Res. Commun.202367513013810.1016/j.bbrc.2023.07.01937473527
     [Google Scholar]
  43. IovaO.M. MarinG.E. LazarI. StanescuI. DogaruG. NiculaC.A. BulboacăA.E. Nitric oxide/nitric oxide synthase system in the pathogenesis of neurodegenerative disorders-An overview.Antioxidants202312375310.3390/antiox1203075336979000
     [Google Scholar]
  44. TolosaA. ZhouX. SpittauB. KrieglsteinK. Establishment of a survival and toxic cellular model for Parkinson’s disease from chicken mesencephalon.Neurotox. Res.201324211912910.1007/s12640‑012‑9367‑y23238634
     [Google Scholar]
  45. BaiL. ChangH.M. ZhangL. ZhuY.M. LeungP.C.K. BMP2 increases the production of BDNF through the upregulation of proBDNF and furin expression in human granulosa-lutein cells.FASEB J.20203412161291614310.1096/fj.202000940R33047388
     [Google Scholar]
  46. CanossaM. GiordanoE. CappelloS. GuarnieriC. FerriS. Nitric oxide down-regulates brain-derived neurotrophic factor secretion in cultured hippocampal neurons.Proc. Natl. Acad. Sci. USA20029953282328710.1073/pnas.04250429911867712
     [Google Scholar]
  47. SinghR. ZahraW. SinghS.S. BirlaH. RathoreA.S. KeshriP.K. DilnashinH. SinghS. SinghS.P. Oleuropein confers neuroprotection against rotenone-induced model of Parkinson’s disease via BDNF/CREB/Akt pathway.Sci. Rep.2023131245210.1038/s41598‑023‑29287‑436774383
     [Google Scholar]
  48. DingY.M. JaumotteJ.D. SignoreA.P. ZigmondM.J. Effects of 6-hydroxydopamine on primary cultures of substantia nigra: Specific damage to dopamine neurons and the impact of glial cell line‐derived neurotrophic factor.J. Neurochem.200489377678710.1111/j.1471‑4159.2004.02415.x15086533
     [Google Scholar]
  49. YinJ. ChangH.M. YiY. YaoY. LeungP.C.K. TGF-β1 increases GDNF production by upregulating the expression of GDNF and furin in human granulosa-lutein cells.Cells20209118510.3390/cells901018531936902
     [Google Scholar]
  50. ViticZ. SaforyH. JovanovicV.M. SarusiY. StavskyA. KahnJ. KuzminaA. TokerL. GitlerD. TaubeR. FriedelR.H. EngelenderS. BrodskiC. BMP5/7 protect dopaminergic neurons in an α-synuclein mouse model of Parkinson’s disease.Brain20211442e1510.1093/brain/awaa36833253359
     [Google Scholar]
  51. WangD. LangZ.C. WeiS.N. WangW. ZhangH. Targeting brain-derived neurotrophic factor in the treatment of neurodegenerative diseases: A review.Neuroprotection20242210.1002/nep3.43.
     [Google Scholar]
  52. Cintrón-ColónA.F. Almeida-AlvesG. BoyntonA.M. SpitsbergenJ.M. GDNF synthesis, signaling, and retrograde transport in motor neurons.Cell Tissue Res.20203821475610.1007/s00441‑020‑03287‑632897420
     [Google Scholar]
  53. YangF. FengL. ZhengF. JohnsonS.W. DuJ. ShenL. WuC. LuB. GDNF acutely modulates excitability and A-type K+ channels in midbrain dopaminergic neurons.Nat. Neurosci.20014111071107810.1038/nn73411593232
     [Google Scholar]
  54. SchlenkerB. MatiasekK. SaurD. GratzkeC. BauerR.M. HerouyY. ArndtC. BleschA. HartungR. StiefC.G. WeidnerN. MayF. Effects of cavernous nerve reconstruction on expression of nitric oxide synthase isoforms in rats.BJU Int.2010106111726173110.1111/j.1464‑410X.2010.09364.x20438559
     [Google Scholar]
  55. KimS.J. RyuM.J. HanJ. JangY. KimJ. LeeM.J. RyuI. JuX. OhE. ChungW. KweonG.R. HeoJ.Y. Activation of the HMGB1-RAGE axis upregulates TH expression in dopaminergic neurons via JNK phosphorylation.Biochem. Biophys. Res. Commun.2017493135836410.1016/j.bbrc.2017.09.01728887039
     [Google Scholar]
  56. TavakolS. MusaviS.M.M. TavakolB. HoveiziE. AiJ. RezayatS.M.J.M.n. Noggin along with a self-assembling peptide nanofiber containing long motif of laminin induces tyrosine hydroxylase gene expression.Mol. Neurobiol.20175464609461610.1007/s12035‑016‑0006‑0.
     [Google Scholar]
  57. Mendes-PinheiroB. Soares-CunhaC. MaroteA. Loureiro-CamposE. CamposJ. Barata-AntunesS. Monteiro-FernandesD. SantosD. Duarte-SilvaS. PintoL. José SalgadoA. Unilateral intrastriatal 6-hydroxydopamine lesion in mice: A closer look into non-motor phenotype and glial response.Int. J. Mol. Sci.202122211153010.3390/ijms22211153034768962
     [Google Scholar]
  58. GlajchK.E. FlemingS.M. SurmeierD.J. OstenP. Sensorimotor assessment of the unilateral 6-hydroxydopamine mouse model of Parkinson’s disease.Behav. Brain Res.2012230230931610.1016/j.bbr.2011.12.00722178078
     [Google Scholar]
  59. Eyhani-RadS. Mohajjel NayebiA. MahmoudiJ. SaminiM. BabapourV. Role of 5-Hydroxytryptamine 1A receptors in 6-hydroxydopmaine-induced catalepsy-like immobilization in rats: A therapeutic approach for treating catalepsy of Parkinson’s disease.Iran. J. Pharm. Res.20121141175118124250551
     [Google Scholar]
  60. Periodic Reporting for period 1 - BMPARK (Development of BMP2 Neurotrophic Therapy for Parkinson’s Disease).Available from: https://cordis.europa.eu/project/id/890290/reporting
  61. TokugawaK. YamamotoK. NishiguchiM. SekineT. SakaiM. UekiT. ChakiS. OkuyamaS. XIB4035, a novel nonpeptidyl small molecule agonist for GFRα-1.Neurochem. Int.2003421818610.1016/S0197‑0186(02)00053‑012441171
     [Google Scholar]
  62. BespalovM.M. SidorovaY.A. SuleymanovaI. ThompsonJ. KamburO. JokinenV. LiliusT. KarelsonG. PuuseppL. RauhalaP. Novel agonist of GDNF family ligand receptor RET for the treatment of experimental neuropathy.BioRxiv201606182010.1101/061820
     [Google Scholar]
  63. SidorovaY.A. BespalovM.M. WongA.W. KamburO. JokinenV. LiliusT.O. SuleymanovaI. KarelsonG. RauhalaP.V. KarelsonM. OsborneP.B. KeastJ.R. KalsoE.A. SaarmaM. A novel small molecule GDNF receptor RET agonist, BT13, promotes neurite growth from sensory neurons in vitro and attenuates experimental neuropathy in the rat.Front. Pharmacol.2017836510.3389/fphar.2017.0036528680400
     [Google Scholar]
  64. RenkoJ.M. MahatoA.K. VisnapuuT. ValkonenK. KarelsonM. VoutilainenM.H. SaarmaM. TuominenR.K. SidorovaY.A. Neuroprotective potential of a small molecule RET agonist in cultured dopamine neurons and hemiparkinsonian rats.J. Parkinsons Dis.20211131023104610.3233/JPD‑20240034024778
     [Google Scholar]
  65. KleinP. Functions of GDNF/Ret signaling in models of autosomal recessive Parkinson’s disease.Thesis, Ludwig Maximilian University of Munich2012
     [Google Scholar]
  66. Hidalgo-FigueroaM. BonillaS. GutiérrezF. PascualA. López-BarneoJ. GDNF is predominantly expressed in the PV+ neostriatal interneuronal ensemble in normal mouse and after injury of the nigrostriatal pathway.J. Neurosci.201232386487210.1523/JNEUROSCI.2693‑11.201222262884
     [Google Scholar]
  67. KasangaE.A. HanY. NavarreteW. McManusR. ShiffletM.K. ParryC. BarahonaA. ManfredssonF.P. NejtekV.A. RichardsonJ.R. SalvatoreM.F. Differential expression of RET and GDNF family receptor, GFR-α1, between striatum and Substantia nigra following nigrostriatal lesion: A case for diminished GDNF-signaling.Exp. Neurol.202336611443510.1016/j.expneurol.2023.11443537178997
     [Google Scholar]
  68. Duarte AzevedoM. SanderS. TenenbaumL. GDNF, A neuron-derived factor upregulated in glial cells during disease.J. Clin. Med.20209245610.3390/jcm902045632046031
     [Google Scholar]
  69. KitsisR.N. LeinwandL.A. Discordance between gene regulation in vitro and in vivo .Gene Expr.1992243133181472867
     [Google Scholar]
  70. Delgado-MinjaresK.M. Martinez-FongD. Martínez-DávilaI.A. BañuelosC. Gutierrez-CastilloM.E. Blanco-AlvarezV.M. Cardenas-AguayoM.C. Luna-MuñozJ. Pacheco-HerreroM. Soto-RojasL.O. Mechanistic insight from preclinical models of Parkinson’s disease could help redirect clinical trial efforts in GDNF therapy.Int. J. Mol. Sci.202122211170210.3390/ijms22211170234769132
     [Google Scholar]
  71. KramerE.R. ConwayJ.A. Is activation of GDNF/RET signaling the answer for successful treatment of Parkinson’s disease? A discussion of data from the culture dish to the clinic.Neural Regen. Res.20221771462146710.4103/1673‑5374.32733034916419
     [Google Scholar]
  72. OjedaV. FuentealbaJ.A. GalleguillosD. AndrésM.E. Rapid increase of Nurr1 expression in the substantia nigra after 6-hydroxydopamine lesion in the striatum of the rat.J. Neurosci. Res.200373568669710.1002/jnr.1070512929136
     [Google Scholar]
  73. CollinsL.M. GouldingS.R. SullivanA.M. O’KeeffeG.W. The potential of bone morphogenetic protein 2 as a neurotrophic factor for Parkinson’s disease.Neural Regen. Res.20201581432143610.4103/1673‑5374.27432731997802
     [Google Scholar]
  74. O’KeeffeG.W. HegartyS.V. SullivanA.M. Targeting bone morphogenetic protein signalling in midbrain dopaminergic neurons as a therapeutic approach in Parkinson’s disease.Neuronal Signal.201712NS2017002710.1042/NS2017002732714578
     [Google Scholar]
  75. Reyes-CoronaD. Vázquez-HernándezN. EscobedoL. Orozco-BarriosC.E. Ayala-DavilaJ. MorenoM.G. Amaro-LaraM.E. Flores-MartinezY.M. Espadas-AlvarezA.J. Fernandez-ParrillaM.A. Gonzalez-BarriosJ.A. Gutierrez-CastilloM.E. González-BurgosI. Martinez-FongD. Neurturin overexpression in dopaminergic neurons induces presynaptic and postsynaptic structural changes in rats with chronic 6-hydroxydopamine lesion.PLoS One20171211e018823910.1371/journal.pone.018823929176874
     [Google Scholar]
  76. SidorovaY.A. VolchoK.P. SalakhutdinovN.F. Neuroregeneration in Parkinson’s disease: from proteins to small molecules.Curr. Neuropharmacol.201917326828710.2174/1570159X1666618090509412330182859
     [Google Scholar]
  77. IvanovaL. Tammiku-TaulJ. SidorovaY. SaarmaM. KarelsonM. Small-molecule ligands as potential GDNF family receptor agonists.ACS Omega2018311022103010.1021/acsomega.7b0193230023796
     [Google Scholar]
  78. AnandA. JainM. ShahA. MedhiB. Discovery of novel small molecule inhibitors targeting progranulin-sortilin: A virtual high throughput screening approach.Res Sq202310.21203/rs.3.rs‑2559741/v1
     [Google Scholar]
  79. JinW. Regulation of BDNF-TrkB signaling and potential therapeutic strategies for Parkinson’s disease.J. Clin. Med.20209125710.3390/jcm901025731963575
     [Google Scholar]
  80. ChitranshiN. GuptaV. DheerY. GuptaV. Vander WallR. GrahamS. Molecular determinants and interaction data of cyclic peptide inhibitor with the extracellular domain of TrkB receptor.Data Brief2016677678210.1016/j.dib.2016.01.01626909388
     [Google Scholar]
  81. NikolausS. WittsackH.J. BeuM. AntkeC. HautzelH. WickrathF. Müller-LutzA. De Souza SilvaM.A. HustonJ.P. AntochG. MüllerH.W. Amantadine enhances nigrostriatal and mesolimbic dopamine function in the rat brain in relation to motor and exploratory activity.Pharmacol. Biochem. Behav.201917915617010.1016/j.pbb.2018.12.01030639878
     [Google Scholar]
  82. CaroffS.N. JainR. MorleyJ.F. Revisiting amantadine as a treatment for drug-induced movement disorders.Ann. Clin. Psychiatry202032319820832722730
     [Google Scholar]
  83. RascolO. FabbriM. PoeweW. Amantadine in the treatment of Parkinson’s disease and other movement disorders.Lancet Neurol.202120121048105610.1016/S1474‑4422(21)00249‑034678171
     [Google Scholar]
  84. FengL. CookB. TsaiS.Y. ZhouT. LaFlammeB. EvansT. ChenS. Discovery of a small-molecule BMP sensitizer for human embryonic stem cell differentiation.Cell Rep.20161592063207510.1016/j.celrep.2016.04.06627210748
     [Google Scholar]
  85. TagliaferroP. BurkeR.E. Retrograde axonal degeneration in Parkinson disease.J. Parkinsons Dis.20166111510.3233/JPD‑15076927003783
     [Google Scholar]
/content/journals/cmc/10.2174/0109298673329597241006053718
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Unveiling the Therapeutic Potential of Small Molecule of SVAK-12: A Comprehensive <span class="jp-italic">In Silico</span>, <span class="jp-italic">In Vitro</span>, and <span class="jp-italic">&nbsp;In Vivo</span> Studies on its Neuroprotective Effects and Molecular Interactions in Parkinson's Disease
Curr. Med. Chem. 32, 9496 (2025); https://doi.org/10.2174/0109298673329597241006053718
/content/journals/cmc/10.2174/0109298673329597241006053718
/content/journals/cmc/10.2174/0109298673329597241006053718
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  • Article Type:     Research Article
Keyword(s): molecular docking; neurotoxicity; neurotrophic factors; Parkinson's disease; Small molecule; SVAK-12

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