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

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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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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Anaemia with Inappropriately Low Erythropoietin in a New Autonomic and Sensory Neuropathy Attributed to Nerve Growth Factor Deficiency

Clinical Science ◽

10.1042/cs080016pa ◽

1991 ◽

Vol 80 (s24) ◽

pp. 16P-16P ◽

Cited By ~ 2

Author(s):

P Anand ◽

P Mary Cotes ◽

P Rudge

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Sensory Neuropathy ◽

Nerve Growth ◽

Factor Deficiency

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A phase II trial of nerve growth factor for sensory neuropathy associated with HIV infection

Neurology ◽

10.1212/wnl.55.1.162 ◽

2000 ◽

Vol 55 (1) ◽

pp. 162-162

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Hiv Infection ◽

Phase Ii ◽

Phase Ii Trial ◽

Sensory Neuropathy ◽

Nerve Growth

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Nerve Growth Factor, Stress and Diseases

Current Medicinal Chemistry ◽

10.2174/0929867327999200818111654 ◽

2020 ◽

Vol 27 ◽

Author(s):

Flavio Maria Ceci ◽

Giampiero Ferraguti ◽

Carla Petrella ◽

Antonio Greco ◽

Paola Tirassa ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Metabolic Disorders ◽

Depressive Disorders ◽

Stressful Events ◽

Stress System ◽

Nerve Growth ◽

Review Reports ◽

Differentiation And Proliferation ◽

Peripheral Sensory

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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