Integral Characterization of Defective BDNF/TrkB Signalling in Neurological and Psychiatric Disorders Leads the Way to New Therapies

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2017 Jan 31

PMID 28134845

Citations 55

Authors

Gonzalo S Tejeda

Margarita Diaz-Guerra

Affiliations

Soon will be listed here.

Abstract

Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated. This review highlights the relevance of an integrative characterization of aberrant BDNF/TrkB pathways for the rational design of therapies that by combining BDNF and TrkB targets could efficiently promote neurotrophic signalling.

Citing Articles

Decoding the Role of Neurotrophins in Glycogen Synthase Kinase 3-Beta Regulation in Alzheimer's Disease.

Rahmatkar S, Singh D Mol Neurobiol. 2025; .

PMID: 40014269 DOI: 10.1007/s12035-025-04776-x.

Semen Cuscutae flavonoids activated the cAMP-PKA-CREB-BDNF pathway and exerted an antidepressant effect in mice.

Shao Q, Li Y, Jin L, Zhou S, Fu X, Liu T Front Pharmacol. 2024; 15:1491900.

PMID: 39654620 PMC: 11625582. DOI: 10.3389/fphar.2024.1491900.

The therapeutic potential of traditional Chinese medicine in depression: focused on the modulation of neuroplasticity.

Lv S, Yang N, Lu Y, Zhang G, Zhong X, Cui Y Front Pharmacol. 2024; 15:1426769.

PMID: 39253375 PMC: 11381291. DOI: 10.3389/fphar.2024.1426769.

BDNF-TrkB Signaling in Mitochondria: Implications for Neurodegenerative Diseases.

K Soman S, Swain M, Dagda R Mol Neurobiol. 2024; 62(2):1756-1769.

PMID: 39030441 PMC: 11909598. DOI: 10.1007/s12035-024-04357-4.

Huanglian Wendan Decoction Improves Insomnia in Rats by Regulating BDNF/TrkB Signaling Pathway Through Gut Microbiota-Mediated SCFAs and Affecting Microglia Polarization.

Shi M, Yang J, Liu Y, Zhao H, Li M, Yang D Mol Neurobiol. 2024; 62(1):1047-1066.

PMID: 38954253 DOI: 10.1007/s12035-024-04330-1.

References

Huang S, Zhao L, Sun Z, Li X, Geng Z, Zhang K . Essential role of Hrs in endocytic recycling of full-length TrkB receptor but not its isoform TrkB.T1. J Biol Chem. 2009; 284(22):15126-36. PMC: 2685694. DOI: 10.1074/jbc.M809763200. View

Liang Z, Liu F, Grundke-Iqbal I, Iqbal K, Gong C . Down-regulation of cAMP-dependent protein kinase by over-activated calpain in Alzheimer disease brain. J Neurochem. 2007; 103(6):2462-70. PMC: 2262109. DOI: 10.1111/j.1471-4159.2007.04942.x. View

Peng X, Peng X, Tehranian R, Dietrich P, Stefanis L, Perez R . Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. J Cell Sci. 2005; 118(Pt 15):3523-30. DOI: 10.1242/jcs.02481. View

von Bohlen Und Halbach O, Minichiello L, Unsicker K . Haploinsufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra. FASEB J. 2005; 19(12):1740-2. DOI: 10.1096/fj.05-3845fje. View

Molander-Melin M, Blennow K, Bogdanovic N, Dellheden B, Mansson J, Fredman P . Structural membrane alterations in Alzheimer brains found to be associated with regional disease development; increased density of gangliosides GM1 and GM2 and loss of cholesterol in detergent-resistant membrane domains. J Neurochem. 2004; 92(1):171-82. DOI: 10.1111/j.1471-4159.2004.02849.x. View

Duman R, Monteggia L . A neurotrophic model for stress-related mood disorders. Biol Psychiatry. 2006; 59(12):1116-27. DOI: 10.1016/j.biopsych.2006.02.013. View

Ohira K, Shimizu K, Hayashi M . Change of expression of full-length and truncated TrkBs in the developing monkey central nervous system. Brain Res Dev Brain Res. 1999; 112(1):21-9. DOI: 10.1016/s0165-3806(98)00151-5. View

Narisawa-Saito M, Wakabayashi K, Tsuji S, Takahashi H, Nawa H . Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimer's disease. Neuroreport. 1996; 7(18):2925-8. DOI: 10.1097/00001756-199611250-00024. View

Vilar M, Mira H . Regulation of Neurogenesis by Neurotrophins during Adulthood: Expected and Unexpected Roles. Front Neurosci. 2016; 10:26. PMC: 4746328. DOI: 10.3389/fnins.2016.00026. View

10.

Zhao L, Mattsson B, Johansson B . Environmental influence on brain-derived neurotrophic factor messenger RNA expression after middle cerebral artery occlusion in spontaneously hypertensive rats. Neuroscience. 2000; 97(1):177-84. DOI: 10.1016/s0306-4522(00)00023-3. View

11.

Liot G, Zala D, Pla P, Mottet G, Piel M, Saudou F . Mutant Huntingtin alters retrograde transport of TrkB receptors in striatal dendrites. J Neurosci. 2013; 33(15):6298-309. PMC: 6619069. DOI: 10.1523/JNEUROSCI.2033-12.2013. View

12.

Colin E, Zala D, Liot G, Rangone H, Borrell-Pages M, Li X . Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J. 2008; 27(15):2124-34. PMC: 2516882. DOI: 10.1038/emboj.2008.133. View

13.

Jin N, Qian W, Yin X, Zhang L, Iqbal K, Grundke-Iqbal I . CREB regulates the expression of neuronal glucose transporter 3: a possible mechanism related to impaired brain glucose uptake in Alzheimer's disease. Nucleic Acids Res. 2013; 41(5):3240-56. PMC: 3597642. DOI: 10.1093/nar/gks1227. View

14.

Chalecka-Franaszek E, Chuang D . Lithium activates the serine/threonine kinase Akt-1 and suppresses glutamate-induced inhibition of Akt-1 activity in neurons. Proc Natl Acad Sci U S A. 1999; 96(15):8745-50. PMC: 17587. DOI: 10.1073/pnas.96.15.8745. View

15.

Deinhardt K, Salinas S, Verastegui C, Watson R, Worth D, Hanrahan S . Rab5 and Rab7 control endocytic sorting along the axonal retrograde transport pathway. Neuron. 2006; 52(2):293-305. DOI: 10.1016/j.neuron.2006.08.018. View

16.

Kao P, Banigan M, Vanderburg C, McKee A, Polgar P, Seshadri S . Increased expression of TrkB and Capzb2 accompanies preserved cognitive status in early Alzheimer disease pathology. J Neuropathol Exp Neurol. 2012; 71(7):654-64. PMC: 3398703. DOI: 10.1097/NEN.0b013e31825d06b7. View

17.

Benisty S, Boissiere F, Faucheux B, Agid Y, Hirsch E . trkB messenger RNA expression in normal human brain and in the substantia nigra of parkinsonian patients: an in situ hybridization study. Neuroscience. 1998; 86(3):813-26. DOI: 10.1016/s0306-4522(98)00126-2. View

18.

Ivanov A, Pellegrino C, Rama S, Dumalska I, Salyha Y, Ben-Ari Y . Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons. J Physiol. 2006; 572(Pt 3):789-98. PMC: 1779993. DOI: 10.1113/jphysiol.2006.105510. View

19.

Fahnestock M, Garzon D, Holsinger R, Michalski B . Neurotrophic factors and Alzheimer's disease: are we focusing on the wrong molecule?. J Neural Transm Suppl. 2002; (62):241-52. DOI: 10.1007/978-3-7091-6139-5_22. View

20.

Gamir-Morralla A, Lopez-Menendez C, Ayuso-Dolado S, Tejeda G, Montaner J, Rosell A . Development of a neuroprotective peptide that preserves survival pathways by preventing Kidins220/ARMS calpain processing induced by excitotoxicity. Cell Death Dis. 2015; 6:e1939. PMC: 4632323. DOI: 10.1038/cddis.2015.307. View