Nerve Growth Factor, Stress and Diseases

Stress is a constant threat for homeostasis and is represented by different extrinsic and intrinsic stimuli (stressors, Hans Selye's "noxious agents"), such as aggressive behavior, fear, diseases, physical activity, drugs, surgical injury, and environmental and physiological changes. Our organism responds to stress activating the adaptive stress system to activate compensatory responses for restoring homeostasis. Nerve Growth Factor (NGF) was discovered as a signaling molecule involved in survival, protection, differentiation, and proliferation of sympathetic and peripheral sensory neurons. NGF mediates stress with an important role in translating environmental stimuli into physiological and pathological feedbacks since NGF levels undergo important variations after exposure to stressful events. Psychological stress, lifestyle stress, and oxidative stress are well known to increase the risk of mental disorders such as schizophrenia, major depressive disorders, bipolar disorder, alcohol use disorders and metabolic disorders such as metabolic syndrome. This review reports recent works describing the activity of NGF in mental and metabolic disorders related to stress.

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Nerve growth factor (NGF) influences differentiation and proliferation of myogenic cells in vitro via TrKA

International Journal of Developmental Neuroscience ◽

10.1016/s0736-5748(00)00041-1 ◽

2000 ◽

Vol 18 (8) ◽

pp. 869-885 ◽

Cited By ~ 56

Author(s):

Mario Rende ◽

Emanuela Brizi ◽

Jim Conner ◽

Susan Treves ◽

Kathrin Censier ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Myogenic Cells ◽

Nerve Growth ◽

Differentiation And Proliferation

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Similarities in development of substance P and somatostatin in peripheral sensory neurons: effects of capsaicin and nerve growth factor.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.78.7.4644 ◽

1981 ◽

Vol 78 (7) ◽

pp. 4644-4647 ◽

Cited By ~ 56

Author(s):

J. A. Kessler ◽

I. B. Black

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Substance P ◽

Sensory Neurons ◽

Nerve Growth ◽

Peripheral Sensory Neurons ◽

Peripheral Sensory

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A missense point mutation in nerve growth factor (NGFR100W) results in selective peripheral sensory neuropathy

Progress in Neurobiology ◽

10.1016/j.pneurobio.2020.101886 ◽

2020 ◽

Vol 194 ◽

pp. 101886

Author(s):

Wanlin Yang ◽

Kijung Sung ◽

Wei Xu ◽

Maria J Rodriguez ◽

Andrew C. Wu ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Point Mutation ◽

Sensory Neuropathy ◽

Peripheral Sensory Neuropathy ◽

Nerve Growth ◽

Peripheral Sensory

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A Missense Point Mutation in Nerve Growth Factor (NGFR100W) Results in Selective Peripheral Sensory Neuropathy

10.1101/784660 ◽

2019 ◽

Author(s):

Wanlin Yang ◽

Kijung Sung ◽

Wei Xu ◽

Maria J Rodriguez ◽

Andrew C. Wu ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Point Mutation ◽

Pain Perception ◽

Nerve Fibers ◽

Anterior Cingulate ◽

Myelinated Nerve ◽

Nerve Growth ◽

Progressive Loss ◽

Peripheral Sensory

ABSTRACTA missense point mutation in nerve growth factor (NGFR100W) is associated with hereditary sensory autonomic neuropathy V (HSAN V), originally discovered in a Swedish family. These patients develop severe loss of perception to deep pain but with apparently normal cognitive functions. To better understand the disease mechanism, we have generated the first NGFR100Wknockin mouse model of HSAN V. Mice homozygous for the NGFR100Wmutation (NGFfln/fln) showed significant structural deficits in intra-epidermal nerve fibers (IENFs) at birth. These mice had a total loss of pain perception at ∼2 months of age and they often failed to survive to full adulthood. Heterozygous mice (NGF+/fln) developed a progressive degeneration of small sensory fibers both behaviorally and functionally: they showed a progressive loss of IENFs starting at the age of 9 months accompanied with progressive loss of perception to painful stimuli such as noxious temperature. Quantitative analysis of lumbar 4/5 dorsal root ganglia (DRG) revealed a significant reduction in small size neurons positive for calcitonin gene-related peptide, while analysis of sciatic nerve fibers revealed the mutant NGF+/flnmice had no reduction in myelinated nerve fibers. Significantly, the amount of NGF secreted from fibroblasts were reduced in heterozygous and homozygous mice compared to their wild-type littermates. Interestingly, NGF+/flnshowed no apparent structural alteration in the brain: neither the anterior cingulate cortex nor the medial septum including NGF-dependent basal forebrain cholinergic neurons. Accordingly, these animals did not develop appreciable deficits in tests for central nervous system function. Our study provides novel insights into the selective impact of NGFR100Wmutation on the development and function of the peripheral sensory system.

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Nerve growth factor and epidermal growth factor stimulate clusterin gene expression in PC12 cells

Biochemical Journal ◽

10.1042/bj3390759 ◽

1999 ◽

Vol 339 (3) ◽

pp. 759-766 ◽

Cited By ~ 19

Author(s):

Claudia GUTACKER ◽

Gerd KLOCK ◽

Patrick DIEL ◽

Claudia KOCH-BRANDT

Keyword(s):

Gene Expression ◽

Nerve Growth Factor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Neuronal Differentiation ◽

Pc12 Cells ◽

Binding Studies ◽

Nerve Growth ◽

Epidermal Growth ◽

Differentiation And Proliferation

Clusterin (apolipoprotein J) is an extracellular glycoprotein that might exert functions in development, cell death and lipid transport. Clusterin gene expression is elevated at sites of tissue remodelling, such as differentiation and apoptosis; however, the signals responsible for this regulation have not been identified. We use here the clusterin gene as a model system to examine expression in PC12 cells under the control of differentiation and proliferation signals produced by nerve growth factor (NGF) and by epidermal growth factor (EGF) respectively. NGF induced clusterin mRNA, which preceded neurite outgrowth typical of neuronal differentiation. EGF also activated the clusterin mRNA, demonstrating that both proliferation and differentiation signals regulate the gene. To localize NGF- and EGF-responsive elements we isolated the clusterin promoter and tested it in PC12 cell transfections. A 2.5 kb promoter fragment and two 1.5 and 0.3 kb deletion mutants were inducible by NGF and EGF. The contribution to this response of a conserved activator protein 1 (AP-1) motif located in the 0.3 kb fragment was analysed by mutagenesis. The mutant promoter was not inducible by NGF or EGF, which identifies the AP-1 motif as an element responding to both factors. Binding studies with PC12 nuclear extracts showed that AP-1 binds to this sequence in the clusterin promoter. These findings suggest that NGF and EGF, which give differential gene regulation in PC12 cells, resulting in neuronal differentiation and proliferation respectively, use the common Ras/extracellular signal-regulated kinase/AP-1 signalling pathway to activate clusterin expression.

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