Journey of brain-derived neurotrophic factor: from intracellular trafficking to secretion

Kojima, Masami; Ishii, Chiaki; Sano, Yoshitake; Mizui, Toshiyuki; Furuichi, Teiichi

doi:10.1007/s00441-020-03274-x

Cited by 18 publications

(15 citation statements)

References 78 publications

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“…Mainly expressed in neurons U n c o r r e c t e d A u t h o r P r o o f through the endoplasmic reticulum (ER) and trans-Golgi network (TGN), before release as the mature BDNF. The complexity of BDNF processing before release involves both independent and integrated steps that are regulated at multiple stages, and has been well described by several investigations [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

The BDNF Val66Met Polymorphism is a Relevant, But not Determinant, Risk Factor in the Etiology of Neuropsychiatric Disorders – Current Advances in Human Studies: A Systematic Review

Assis

Hoffman

2022

BPL

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Brain-derived neurotrophic factor (BDNF) is the brain’s most-produced neurotrophin during the lifespan, essentially involved in multiple mechanisms of nervous system development and function. The production/release of BDNF requires multi-stage processing that appears to be regulated at various stages in which the presence of a polymorphism “Val66Met” can exert a critical influence. Aim: To synthesize the knowledge on the BDNF Val66Met polymorphism on intracellular processing and function of BDNF. Methods: We performed a systematic review and collected all available studies on the post-translation processes of BDNF, regarding the Val66Met polymorphism. Searches were performed up to 21st March 2021. Results: Out of 129 eligible papers, 18 studies addressed or had findings relating to BDNF post-translation processes and were included in this review. Discussion: Compilation of experimental findings reveals that the Val66Met polymorphism affects BDNF function by slightly altering the processing, distribution, and regulated release of BDNF. Regarding the critical role of pro-BDNF as a pro-apoptotic factor, such alteration might represent a risk for the development of neuropsychiatric disorders.

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Section: Introductionmentioning

confidence: 99%

The BDNF Val66Met Polymorphism is a Relevant, But not Determinant, Risk Factor in the Etiology of Neuropsychiatric Disorders – Current Advances in Human Studies: A Systematic Review

Assis

Hoffman

2022

BPL

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“…The present results also show that the Bdnf mRNA level was unchanged in the denervated midbrain, but that the level of mature BDNF protein was upregulated (Figure 6C). It is known that proBDNF is released extracellularly (Yang et al, 2009), and post-transcriptional modification of proBDNF mediated by plasminogen activators has been implicated in various neuronal functions, such as long-term potentiation and long-term memory (Pang et al, 2004; Kojima et al, 2020b). Thus, we speculate that plasminogen activators upregulated in the denervated midbrain promote the extracellular cleavage of proBDNF and production of mature BDNF.…”

Section: Discussionmentioning

confidence: 99%

Involvement of denervated midbrain-derived factors in the formation of ectopic cortico-mesencephalic projection after hemispherectomy

Chang

Masada

Kojima

et al. 2021

Preprint

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Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain to compensate for the lost function, but the underlying molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at P6, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by astrocytes or microglia. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit beta 3 (Itgb3) or neurotrophic receptor tyrosine kinase 2 (Ntrk2, also known as TrkB) was knocked out. Overall, the present study suggests that midbrain-derived glial factors whose expression is upregulated after hemispherectomy are involved in lesion-induced remodeling of the cortico-mesencephalic projection.

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“…9A). It is known that proBDNF is released extracellularly (Yang et al, 2009), and posttranscriptional modification of proBDNF mediated by plasminogen activators has been implicated in various aspects of neural plasticity (Lee et al, 2001;Mataga et al, 2004;Pang et al, 2004;Kojima et al, 2020b). Thus, it is likely that plasminogen activators upregulated in the denervated midbrain promote the extracellular cleavage of proBDNF and production of mature BDNF.…”

Section: Discussionmentioning

confidence: 99%

Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy

et al. 2021

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Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit b three or neurotrophic receptor tyrosine kinase 2 (also known as TrkB) was knocked out. Overall, the present study suggests that denervated midbrain-derived glial factors contribute to lesion-induced remodeling of the cortico-mesencephalic projection via these receptors.

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Journey of brain-derived neurotrophic factor: from intracellular trafficking to secretion

Cited by 18 publications

References 78 publications

The BDNF Val66Met Polymorphism is a Relevant, But not Determinant, Risk Factor in the Etiology of Neuropsychiatric Disorders – Current Advances in Human Studies: A Systematic Review

The BDNF Val66Met Polymorphism is a Relevant, But not Determinant, Risk Factor in the Etiology of Neuropsychiatric Disorders – Current Advances in Human Studies: A Systematic Review

Involvement of denervated midbrain-derived factors in the formation of ectopic cortico-mesencephalic projection after hemispherectomy

Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy

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