Mechanisms and regulation of neurotrophin synthesis and secretion

Qudah, Mohammad Al; Al‐Dwairi, Ahmed

doi:10.17712/nsj.2016.4.20160080

Cited by 41 publications

(34 citation statements)

References 60 publications

(85 reference statements)

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“…ProBDNF is synthesized in the endoplasmic reticulum (ER) and secreted from dense-core vesicles. After packaging into dense-core vesicles, ProBDNF is trafficked through either the regulated secretory pathway or the constitutive secretory pathway [10,11]. ProBDNF is processed to mature BDNF by several alternative cellular mechanisms.…”

Section: Brain-derived Neurotrophic Factormentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Stem Cell-Based Technologies in Huntington’s Disease Therapy

Kerkis¹,

Silva²,

Wenceslau³

et al. 2021

Neurodegenerative Diseases - Molecular Mechanisms and Current Therapeutic Approaches

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Neurodegenerative disorders, such as Huntington's disease (HD), Alzheimer's disease (AD), and Parkinson's disease (PD), are characterized by changes in the levels and activities of neurotrophic factors (NTFs), such as brain-derived neurotrophic factor (BDNF). Gain-of-function and loss-of-function experiments demonstrate in fact the linkage between wild-type huntingtin (HTT) and gene transcription and intracellular transport of BDNF. In the present chapter, we will analyze the involvement of BDNF in HD and other neurodegenerative diseases. We will discuss the current BDNF technologies focusing on stem cell therapies that induce BDNF upregulation, for instance, the method of autologous mesenchymal stem cell (MSC) culturing in the presence of cocktail of BDNF inducers and factors (MSC/BDNF), genetic engineering of MSC and their use as a vector for BDNF gene delivery, and combined method of establishment of embryonic stem cell (ESC)derived BDNF-overexpressing neural progenitors, which is still at the preclinical stage. Clinical trial that uses MSC/BDNF is already in course, while genetic engineering of MSC/BDNF is in perspective to treat adult and juvenile HD. The potential application of these technologies is beyond HD. Other neurodegenerative disorders such as Alzheimer's and Parkinson's diseases also can be further included in the list of clinical trials that use MSC/BDNF or even ESC/BDNF-overexpressing neural progenitors.

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Section: Brain-derived Neurotrophic Factormentioning

confidence: 99%

Brain-Derived Neurotrophic Factor and Stem Cell-Based Technologies in Huntington’s Disease Therapy

Kerkis¹,

Silva²,

Wenceslau³

et al. 2021

Neurodegenerative Diseases - Molecular Mechanisms and Current Therapeutic Approaches

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“…80 The neurotrophic factors including BDNF are produced constitutively or via regulated pathways in non-neural tissues. 81 SNP alters the activity dependent secretion of BDNF which results in reduced BDNF production also it binds with lower affinity to receptor namedp 75NTR . [82][83][84] The Met allele or SNP was reported to damage the intercellular trafficking of BDNF with a nearly 30% reduction of activity dependent secretion of BDNF.…”

Section: Distal Factorsmentioning

confidence: 99%

Social and Biological Parameters Involved in Suicide Ideation During the COVID-19 Pandemic: A Narrative Review

Chenthamara

Prasathkumar

Becky

et al. 2020

Int J�Tryptophan�Res

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Fear is an indispensable characteristic of any infectious disease, and the alarm will be further amplified when the infection spreads uncontrollable, unpredictable, and global. The novel corona virus (SARS CoV-2) lead Covid-19, has been declared as a global emergency by WHO as it has affected millions of people with a high mortality rate. The non-availability of medicine for Covid-19 and the various control measures such as social distancing, self-isolation, house quarantine, and the new normal implementation by different nations across the world to control the spread of Covid-19 made people vulnerable to fear and anxiety. As a result, considerable number of Covid-19-related suicidal deaths has been reported across the world during this pandemic. There have been several studies which describe the psychosocial aspects of suicidal ideation. However, the research on the biological aspects of suicidal ideation/suicidal risk factors that are related to pandemic are unreported. Hence this review article is intended to provide a comprehensive analysis of suicidal deaths during Covid-19 and also aimed to addresses the possible link between suicidal ideation and different factors, including psycho-social, behavioral, neurobiological factors (proximal, distal, and inflammatory) and immunity. The alterations in glutamatergic and GABAergic neurotransmitters had upregulated the GABARB3, GABARA4, GABARA3, GABARR1, GABARG2, and GAD2 gene expressions in suicidal victims. The changes in the Kynurenine (KYN) pathway, Hypothalamus-Pituitary-Adrenal axis (HPA axis) hyperactivation, and dysregulation of serotonin biosynthesis would significantly alter the brain chemistry in people with suicide ideation.

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“…We speculated that yolkin can be CREBdependent cellular signaling activator providing to BDNF expression/production. Endogenously synthetized BDNF is stored and transported in dense core vesicles and secreted at synapses in response to activity [37,38]. Therefore, effect of yolkin on molecular mechanisms regulating BDNF transport and release from synapses is also considered.…”

Section: Researchmentioning

confidence: 99%

Yolkin- A Polypeptide Complex Isolated From Chicken Egg Yolk with Potential Neuroprotective and Antioxidative Activity

Zabłocka¹,

Aleks²,

Zambrowicz³

et al. 2018

Neuropsychiatry

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Background Yolkin, the polypeptide complex isolated from chicken egg yolk as a fraction accompanying immunoglobulin IgY, possess immunoregulatory activity and improves cognitive function of aged rats. However, the mechanism of its action was not clear. In the development of neurodegenerative diseases, the oxidative stress, permanent inflammation and decreased level of neurotrophic factors are included. Therefore the upregulation of the level of neuroprotective factors and activation of antioxidant system are the key manners to control the nervous system function. In this study, we aimed to investigate the effect of polypeptide complex yolkin on brain-derived neurotrophic factor (BDNF) production and on reduction of oxidative stress. Methods In the present study PC12 Tet On cell line and human whole blood were used to investigate the neuroprotective activity of yolkin. Viability of PC12 Tet On cells exposed to various concentrations of yolkin was determined by MTT assay. The level of BDNF released in response to yolkin by both PC12 cells and human whole blood was determined by ELISA. The influence of yolkin on intracellular ROS level was determined using DCFH-DA assay. Antioxidant capacity of yolkin was determined by DPPH assay, FRAP method and FE (II) ion chelation method. Results The results obtained showed that yolkin is not antioxidant but significantly reduces intracellular oxidative stress induced by hydrogen peroxide application. Yolkin also stimulates both PC12 Tet On neuronal cells and cells of human whole blood to release of BDNF in dose-dependent manner. Conclusions Our study showed that the natural origin regulatory substances such as yolkin may be useful as an efficient bioactive compound for the treatment of impairments of central nervous system accompanying neurodegenerative diseases e.g. Alzheimer's and Parkinson's.

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Mechanisms and regulation of neurotrophin synthesis and secretion

Cited by 41 publications

References 60 publications

Brain-Derived Neurotrophic Factor and Stem Cell-Based Technologies in Huntington’s Disease Therapy

Brain-Derived Neurotrophic Factor and Stem Cell-Based Technologies in Huntington’s Disease Therapy

Social and Biological Parameters Involved in Suicide Ideation During the COVID-19 Pandemic: A Narrative Review

Yolkin- A Polypeptide Complex Isolated From Chicken Egg Yolk with Potential Neuroprotective and Antioxidative Activity

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