Cellular and molecular mechanisms of the brain-derived neurotrophic factor in physiological and pathological conditions

2016 ◽  
Vol 131 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Veronica Begni ◽  
Marco Andrea Riva ◽  
Annamaria Cattaneo
Keyword(s):  
Synaptic Plasticity ◽  
Stress Response ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Depressive Disorders ◽  
Brain Derived Neurotrophic Factor ◽  
Mitogen Activated Protein Kinase ◽  
Bdnf Expression ◽  
Pathological Conditions ◽  
Wide Range

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a key role in the central nervous system, promoting synaptic plasticity, neurogenesis and neuroprotection. The BDNF gene structure is very complex and consists of multiple 5′-non-coding exons, which give rise to differently spliced transcripts, and one coding exon at the 3′-end. These multiple transcripts, together with the complex transcriptional regulatory machinery, lead to a complex and fine regulation of BDNF expression that can be tissue and stimulus specific. BDNF effects are mainly mediated by the high-affinity, tropomyosin-related, kinase B receptor and involve the activation of several downstream cascades, including the mitogen-activated protein kinase, phospholipase C-γ and phosphoinositide-3-kinase pathways. BDNF exerts a wide range of effects on neuronal function, including the modulation of activity-dependent synaptic plasticity and neurogenesis. Importantly, alterations in BDNF expression and function are involved in different brain disorders and represent a major downstream mechanism for stress response, which has important implications in psychiatric diseases, such as major depressive disorders and schizophrenia. In the present review, we have summarized the main features of BDNF in relation to neuronal plasticity, stress response and pathological conditions, and discussed the role of BDNF as a possible target for pharmacological and non-pharmacological treatments in the context of psychiatric illnesses.

The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease

2022 ◽  
Vol 0 (0) ◽  
Author(s):  
Shaun Cade ◽  
Xin-Fu Zhou ◽  
Larisa Bobrovskaya
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Synaptic Plasticity ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Neurotrophin Receptor ◽  
Current Evidence ◽  
Synaptic Dysfunction ◽  
Age Related

Abstract Alzheimer’s disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer’s disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer’s disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease’s progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer’s disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer’s disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer’s disease.

Is Brain-Derived Neurotrophic Factor: A Common Link Between Neurodegenerative Disorders and Cancer?

2019 ◽  
Vol 16 (4) ◽  
pp. 344-352
Author(s):  
Radhika Khosla ◽  
Avijit Banik ◽  
Sushant Kaushal ◽  
Priya Battu ◽  
Deepti Gupta ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Neurotrophic Factor ◽  
Animal Studies ◽  
Neurodegenerative Disorder ◽  
Indirect Evidence ◽  
Brain Derived Neurotrophic Factor ◽  
Common Disease ◽  
Inverse Association ◽  
Bdnf Expression ◽  
Strong Inverse Association

Background: Cancer is a common disease caused by the excessive proliferation of cells, and neurodegenerative diseases are the disorders caused due to the degeneration of neurons. Both can be considered as diseases caused by the dysregulation of cell cycle events. A recent data suggests that there is a strong inverse association between cancer and neurodegenerative disorders. There is indirect evidence to postulate Brain-derived Neurotrophic Factor (BDNF) as a potential molecular link in this association. Discussion: The BDNF levels are found to be downregulated in many neurodegenerative disorders and are found to be upregulated in various kinds of cancers. The lower level of BDNF in Alzheimer’s and Parkinson’s disease has been found to be related to cognitive and other neuropsychological impairments, whereas, its higher levels are associated with the tumour growth and metastasis and poor survival rate in the cancer patients. Conclusion: In this review, we propose that variance in BDNF levels is critical in determining the course of cellular pathophysiology and the development of cancer or neurodegenerative disorder. We further propose that an alternative therapeutic strategy that can modulate BDNF expression, can rescue or prevent above said pathophysiological course. Larger studies that examine this link through animal studies are imperative to understand the putative biochemical and molecular link to wellness and disease.

scholarly journals When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4617
Author(s):  
Styliana Kyriakoudi ◽  
Anthi Drousiotou ◽  
Petros P. Petrou
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Disease Development ◽  
Pathological Conditions ◽  
Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

scholarly journals Cellular and molecular mechanisms regulating neuronal growth by brain-derived neurotrophic factor

Cytoskeleton ◽  
2016 ◽  
Vol 73 (10) ◽  
pp. 612-628 ◽  
Author(s):  
Andres Gonzalez ◽  
Guillermo Moya-Alvarado ◽  
Christian Gonzalez-Billaut ◽  
Francisca C. Bronfman
Keyword(s):  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Brain Derived Neurotrophic Factor ◽  
Neuronal Growth

scholarly journals Interferon beta-1a induces expression of brain-derived neurotrophic factor in human T lymphocytes in vitro and not in vivo

2020 ◽  
Vol 15 (1) ◽  
pp. FNL38 ◽  
Author(s):  
Zarlascht Karmand ◽  
Hans-Peter Hartung ◽  
Oliver Neuhaus
Keyword(s):  
T Cell ◽  
Neurotrophic Factor ◽  
Serum Levels ◽  
Brain Derived Neurotrophic Factor ◽  
Peripheral Blood Lymphocytes ◽  
T Cell Proliferation ◽  
Bdnf Expression ◽  
Healthy Donors

Aim: To detect IFN β-1a-induced expression of brain-derived neurotrophic factor (BDNF) to undermine the hypothesis of IFN β-1a-associated neuroprotection in multiple sclerosis (MS). Methods: The influence of IFN β-1a on in vitro activated peripheral blood lymphocytes from healthy donors was tested. Proliferation analyses were made to detect T-cell growth. BDNF expression was measured by standard ELISA. To assess the influence of IFN β-1a on BDNF expression in vivo, BDNF serum levels of MS patients treated with IFN β-1a were compared with those of untreated patients. Results: IFN β-1a inhibited T-cell proliferation dose dependently. It induced BDNF expression at middle concentrations. MS patients treated with IFN β-1a exhibited significantly lower BDNF serum levels than untreated patients. Conclusion: IFN β-1a may promote neuroprotection by inducing BDNF expression, but its importance in vivo remains open.

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