Regulation of BDNF-TrkB Signaling and Potential Therapeutic Strategies for Parkinson's Disease

Overview

Journal J Clin Med

Specialty General Medicine

Date 2020 Jan 23

PMID 31963575

Citations 74

Authors

Wook Jin

Affiliations

Soon will be listed here.

Abstract

Brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-related kinase receptor type B (TrkB) are widely distributed in multiple regions of the human brain. Specifically, BDNF/TrkB is highly expressed and activated in the dopaminergic neurons of the substantia nigra and plays a critical role in neurophysiological processes, including neuro-protection and maturation and maintenance of neurons. The activation as well as dysfunction of the BDNF-TrkB pathway are associated with neurodegenerative diseases. The expression of BDNF/TrkB in the substantia nigra is significantly reduced in Parkinson's Disease (PD) patients. This review summarizes recent progress in the understanding of the cellular and molecular roles of BNDF/TrkB signaling and its isoform, TrkB.T1, in Parkinson's disease. We have also discussed the effects of current therapies on BDNF/TrkB signaling in Parkinson's disease patients and the mechanisms underlying the mutation-mediated acquisition of resistance to therapies for Parkinson's disease.

Citing Articles

The Role of Brain-Derived Neurotrophic Factor as an Essential Mediator in Neuronal Functions and the Therapeutic Potential of Its Mimetics for Neuroprotection in Neurologic and Psychiatric Disorders.

Numakawa T, Kajihara R Molecules. 2025; 30(4).

PMID: 40005159 PMC: 11857940. DOI: 10.3390/molecules30040848.

Relationship between enriched environment and neurodegeneration: a review from mechanism to therapy.

Xu Y, Chen Y, Xing J, Yao J Clin Epigenetics. 2025; 17(1):13.

PMID: 39849536 PMC: 11761206. DOI: 10.1186/s13148-025-01820-4.

Genetic analyses identify circulating genes related to brain structures associated with Parkinson's disease.

Han Z, Zhu Y, Xia Z, Deng Q, He H, Yin Q NPJ Parkinsons Dis. 2025; 11(1):17.

PMID: 39809793 PMC: 11733288. DOI: 10.1038/s41531-024-00859-z.

An Updated Bio-Behavioral Profile of the Flinders Sensitive Line Rat: Reviewing the Findings of the Past Decade.

Steyn S Pharmacol Res Perspect. 2025; 13(1):e70058.

PMID: 39786312 PMC: 11717001. DOI: 10.1002/prp2.70058.

The role of RGC degeneration in the pathogenesis of glaucoma.

Si Z, Fan Y, Wang M, Zhao J, Zhang Y, Liu D Int J Biol Sci. 2025; 21(1):211-232.

PMID: 39744428 PMC: 11667808. DOI: 10.7150/ijbs.103222.

References

Zhang X, Andren P, Svenningsson P . Repeated l-DOPA treatment increases c-fos and BDNF mRNAs in the subthalamic nucleus in the 6-OHDA rat model of Parkinson's disease. Brain Res. 2006; 1095(1):207-10. DOI: 10.1016/j.brainres.2006.04.019. View

Li X, Dai C, Chen L, Zhou W, Han H, Dong Z . 7,8-dihydroxyflavone Ameliorates Motor Deficits Via Suppressing α-synuclein Expression and Oxidative Stress in the MPTP-induced Mouse Model of Parkinson's Disease. CNS Neurosci Ther. 2016; 22(7):617-24. PMC: 6492848. DOI: 10.1111/cns.12555. View

Liebl D, Huang W, Young W, Parada L . Regulation of Trk receptors following contusion of the rat spinal cord. Exp Neurol. 2001; 167(1):15-26. DOI: 10.1006/exnr.2000.7548. View

Luberg K, Wong J, Weickert C, Timmusk T . Human TrkB gene: novel alternative transcripts, protein isoforms and expression pattern in the prefrontal cerebral cortex during postnatal development. J Neurochem. 2010; 113(4):952-64. DOI: 10.1111/j.1471-4159.2010.06662.x. View

Fenner M, Achim C, Fenner B . Expression of full-length and truncated trkB in human striatum and substantia nigra neurons: implications for Parkinson's disease. J Mol Histol. 2013; 45(3):349-61. DOI: 10.1007/s10735-013-9562-z. View

Mizuno M, Yamada K, Olariu A, Nawa H, Nabeshima T . Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats. J Neurosci. 2000; 20(18):7116-21. PMC: 6772840. View

Lin D, Wu Q, Lin X, Borlongan C, He Z, Tan J . Brain-derived Neurotrophic Factor Signaling Pathway: Modulation by Acupuncture in Telomerase Knockout Mice. Altern Ther Health Med. 2015; 21(6):36-46. View

Liu X, Chan C, Jang S, Pradoldej S, Huang J, He K . A synthetic 7,8-dihydroxyflavone derivative promotes neurogenesis and exhibits potent antidepressant effect. J Med Chem. 2010; 53(23):8274-86. PMC: 3150605. DOI: 10.1021/jm101206p. View

Gulyaeva N . Interplay between Brain BDNF and Glutamatergic Systems: A Brief State of the Evidence and Association with the Pathogenesis of Depression. Biochemistry (Mosc). 2017; 82(3):301-307. DOI: 10.1134/S0006297917030087. View

10.

Seroogy K, Lundgren K, Tran T, Guthrie K, Isackson P, Gall C . Dopaminergic neurons in rat ventral midbrain express brain-derived neurotrophic factor and neurotrophin-3 mRNAs. J Comp Neurol. 1994; 342(3):321-34. DOI: 10.1002/cne.903420302. View

11.

Krishna R, Ali M, Moustafa A . Effects of combined MAO-B inhibitors and levodopa vs. monotherapy in Parkinson's disease. Front Aging Neurosci. 2014; 6:180. PMC: 4111079. DOI: 10.3389/fnagi.2014.00180. View

12.

Bunten S, Happe S . Rotigotine transdermal system: a short review. Neuropsychiatr Dis Treat. 2009; 2(4):421-6. PMC: 2671947. DOI: 10.2147/nedt.2006.2.4.421. View

13.

Raupp-Barcaro I, Vital M, Galduroz J, Andreatini R . Potential antidepressant effect of amantadine: a review of preclinical studies and clinical trials. Braz J Psychiatry. 2018; 40(4):449-458. PMC: 6899375. DOI: 10.1590/1516-4446-2017-2393. View

14.

Devi L, Ohno M . TrkB reduction exacerbates Alzheimer's disease-like signaling aberrations and memory deficits without affecting β-amyloidosis in 5XFAD mice. Transl Psychiatry. 2015; 5:e562. PMC: 4471286. DOI: 10.1038/tp.2015.55. View

15.

Choo M, Miyazaki T, Yamazaki M, Kawamura M, Nakazawa T, Zhang J . Retrograde BDNF to TrkB signaling promotes synapse elimination in the developing cerebellum. Nat Commun. 2017; 8(1):195. PMC: 5543168. DOI: 10.1038/s41467-017-00260-w. View

16.

Tronci E, Napolitano F, Munoz A, Fidalgo C, Rossi F, Bjorklund A . BDNF over-expression induces striatal serotonin fiber sprouting and increases the susceptibility to l-DOPA-induced dyskinesia in 6-OHDA-lesioned rats. Exp Neurol. 2017; 297:73-81. DOI: 10.1016/j.expneurol.2017.07.017. View

17.

Pramanik S, Sulistio Y, Heese K . Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy. Mol Neurobiol. 2016; 54(9):7401-7459. DOI: 10.1007/s12035-016-0214-7. View

18.

He J, Xiang Z, Zhu X, Ai Z, Shen J, Huang T . Neuroprotective Effects of 7, 8-dihydroxyflavone on Midbrain Dopaminergic Neurons in MPP-treated Monkeys. Sci Rep. 2016; 6:34339. PMC: 5059638. DOI: 10.1038/srep34339. View

19.

Zhao Q, Cai D, Bai Y . Selegiline rescues gait deficits and the loss of dopaminergic neurons in a subacute MPTP mouse model of Parkinson's disease. Int J Mol Med. 2013; 32(4):883-91. DOI: 10.3892/ijmm.2013.1450. View

20.

Haniu M, Talvenheimo J, Le J, Katta V, WELCHER A, Rohde M . Extracellular domain of neurotrophin receptor trkB: disulfide structure, N-glycosylation sites, and ligand binding. Arch Biochem Biophys. 1995; 322(1):256-64. DOI: 10.1006/abbi.1995.1460. View