Perspective role of Substance P in Amyotrophic Lateral Sclerosis: From neuronal vulnerability to neuroprotection.

The neuropeptide Substance P (SP) and its preferred Neurokinin1 Receptor (NK1R) are known to participate in the physiopathology of neurodegenerative diseases and mainly exert a neuroprotective role. In the present work, we have described the involvement of SP and NK1R in Amyotrophic Lateral Sclerosis (ALS). This was demonstrated by the detection of altered levels of SP in the brain, spinal cord and cerebrospinal fluid (CSF) of patients and preclinical models of ALS, and by its ability to inhibit excitotoxicity-induced neurodegeneration in ALS animal models.

ProNGF processing in adult rat tissues and bioactivity of NGF prodomain peptides.

The neurotrophin nerve growth factor (NGF) and its precursor proNGF are both bioactive and exert similar or opposite actions depending on the cell target and its milieu. The balance between NGF and proNGF is crucial for cell and tissue homeostasis and it is considered an indicator of pathological conditions. Proteolytical cleavage of proNGF to the mature form results in different fragments, whose function and/or bioactivity is still unclear.

Involvement of Substance P (SP) and Its Related NK1 Receptor in Primary Sjögren's Syndrome (pSS) Pathogenesis.

Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that primarily attacks the lacrimal and salivary glands, resulting in impaired secretory function characterized by xerostomia and xerophthalmia. Patients with pSS have been shown to have impaired salivary gland innervation and altered circulating levels of neuropeptides thought to be a cause of decreased salivation, including substance P (SP). Using Western blot analysis and immunofluorescence studies, we examined the expression levels of SP and its preferred G protein-coupled TK Receptor 1 (NK1R) and apoptosis markers in biopsies of the minor salivary gland (MSG) from pSS patients compared with patients with idiopathic sicca syndrome.

Psycho-Cognitive Profile and NGF and BDNF Levels in Tears and Serum: A Pilot Study in Patients with Graves' Disease.

Nerve Growth Factor (NGF) and Brain derived Neurotrophic Factor (BDNF) mature/precursor imbalance in tears and serum is suggested as a risk factor and symptomatology aggravation in ophthalmology and neuropsychiatric disturbances. Cognitive and mood alterations are reported by patients with Graves' Orbitopathy (GO), indicating neurotrophin alterations might be involved. To address this question, the expression levels of NGF and BDNF and their precursors in serum and tears of GO patients were analyzed and correlated with the ophthalmological and psycho-cognitive symptoms.

NGF Prevents Loss of TrkA/VEGFR2 Cells, and VEGF Isoform Dysregulation in the Retina of Adult Diabetic Rats.

Among the factors involved in diabetic retinopathy (DR), nerve growth factor (NGF) and vascular endothelial growth factor A (VEGFA) have been shown to affect both neuronal survival and vascular function, suggesting that their crosstalk might influence DR outcomes. To address this question, the administration of eye drops containing NGF (ed-NGF) to adult Sprague Dawley rats receiving streptozotocin (STZ) intraperitoneal injection was used as an experimental paradigm to investigate NGF modulation of VEGFA and its receptor VEGFR2 expression. We show that ed-NGF treatment prevents the histological and vascular alterations in STZ retina, VEGFR2 expression decreased in GCL and INL, and preserved the co-expression of VEGFR2 and NGF-tropomyosin-related kinase A (TrkA) receptor in retinal ganglion cells (RGCs).

Pilot Investigation on p75ICD Expression in Laryngeal Squamous Cell Carcinoma.

We investigated the p75 Neurotrophin Receptor (p75NTR) expression and cleavage product p75NTR Intracellular Domain (p75ICD) as potential oncogenic and metastatic markers in human Laryngeal Squamous Cell Carcinoma (LSCC). p75NTR is highly expressed in Cancer Stem Cells (CSCs) of the laryngeal epithelia and it has been proposed as a marker for stemness, cell migration, and chemo-resistance in different squamous carcinomas. To investigate the clinical significance of p75NTR cleavage products in solid tumors, full-length and cleaved p75NTR expression was analyzed in laryngeal primary tumors from different-stage LSCC patients, diagnosed at the Policlinico Umberto I Hospital.

Behavioral dysregulations by chronic alcohol abuse. Motivational enhancement therapy and cognitive behavioral therapy outcomes.

Patients with alcohol use disorder (AUD) do not manifest homogeneous clinical symptoms. Various studies described both cognitive impairments and psychiatric disorders among people with AUD. This disorder is one of the most frequent mental disorders in developed countries, due to excessive alcohol consumption.

Gender differences in ultradian serum levels of NGF and BDNF correlate with psychophysical traits in healthy humans.

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.

Markers of Neuroinflammation in the Serum of Prepubertal Children with Fetal Alcohol Spectrum Disorders.

Background: Fetal Alcohol Spectrum Disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with Fetal Alcohol Syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers.

NGF Eye Administration Recovers the TrkB and Glutamate/GABA Marker Deficit in the Adult Visual Cortex Following Optic Nerve Crush.

Eye-drop recombinant human nerve growth factor (ed-rhNGF) has proved to recover the retina and optic nerve damage in animal models, including the unilateral optic nerve crush (ONC), and to improve visual acuity in humans. These data, associated with evidence that ed-rhNGF stimulates the brain derived neurotrophic factor (BDNF) in retina and cortex, suggests that NGF might exert retino-fugal effects by affecting BDNF and its receptor TrkB. To address these questions, their expression and relationship with the GABAergic and glutamatergic transmission markers, GAD65 and GAD67, vesicular inhibitory amino acid transporter (VGAT), and vesicular glutamate transporters 1 and 2 (VGLUT-1 and VGLUT-2) were investigated in adult ONC rats contralateral and ipsilateral visual cortex (VCx).

Vagus nerve stimulation and Neurotrophins: a biological psychiatric perspective.

Since 2004, vagus nerve stimulation (VNS) has been used in treatment-resistant or treatment-intolerant depressive episodes. Today, VNS is suggested as possible therapy for a larger spectrum of psychiatric disorders, including schizophrenia, obsessive compulsive disorders, and panic disorders. Despite a large body of literature supports the application of VNS in patients' treatment, the exact mechanism of action of VNS remains not fully understood.

Topical recombinant human Nerve growth factor (rh-NGF) is neuroprotective to retinal ganglion cells by targeting secondary degeneration.

Optic neuropathy is a major cause of irreversible blindness worldwide, and no effective treatment is currently available. Secondary degeneration is believed to be the major contributor to retinal ganglion cell (RGC) death, the endpoint of optic neuropathy. Partial optic nerve transection (pONT) is an established model of optic neuropathy.

Nerve growth factor in the psychiatric brain.

The nerve growth factor (NGF) belongs to a family of proteins named neurotrophins, consisting of NGF, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), NT-4/5 and NT-6. NGF regulates a large number of physiological mechanisms that result in neurotrophic, metabotrophic and/or immunotrophic effects. Neurodegenerative diseases, including Alzheimer disease, psychiatric disorders (e.

hNGF Peptides Elicit the NGF-TrkA Signalling Pathway in Cholinergic Neurons and Retain Full Neurotrophic Activity in the DRG Assay.

In the last decade, Nerve Growth Factor (NGF)-based clinical approaches have lacked specific and efficient Tyrosine Kinase A (TrkA) agonists for brain delivery. Nowadays, the characterization of novel small peptidomimetic is taking centre stage in preclinical studies, in order to overcome the main size-related limitation in brain delivery of NGF holoprotein for Central Nervous System (CNS) pathologies. Here we investigated the NGF mimetic properties of the human NGF 1-14 sequence (hNGF1-14) and its derivatives, by resorting to primary cholinergic and dorsal root ganglia (DRG) neurons.

Cancer stem cells-driven tumor growth and immune escape: the Janus face of neurotrophins.

Cancer Stem Cells (CSCs) are self-renewing cancer cells responsible for expansion of the malignant mass in a dynamic process shaping the tumor microenvironment. CSCs may hijack the host immune surveillance resulting in typically aggressive tumors with poor prognosis.In this review, we focus on neurotrophic control of cellular substrates and molecular mechanisms involved in CSC-driven tumor growth as well as in host immune surveillance.

VEGF inhibition alters neurotrophin signalling pathways and induces caspase-3 activation and autophagy in rabbit retina.

This study sought to evaluate the prospective role exerted by vascular endothelial growth factor (VEGF) in the modulation of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) signalling pathways in the rabbit retina. To reach this aim, the anti-VEGF agents aflibercept and ranibizumab were used as a pharmacological approach to evaluate the putative consequences elicited by VEGF inhibition on neurotrophin signalling. VEGF inhibition determined a marked imbalance in proneurotrophin expression, a significant reduction in TrkA and TrkB phosphorylation states and a decrease in the pan-neurotrophin receptor p75.

Correction to: The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS Activation.

The authors, due to the change in one of the University name at the affiliation, hereby correct the proof.

In vivo antivascular endothelial growth factor treatment induces corneal endothelium apoptosis in rabbits through changes in p75NTR-proNGF pathway.

Intravitreal injection (IVT) of antivascular endothelial growth factor (anti-VEGF) agents is widely used for the treatment of retinal vascular diseases. Recently, the injection of anti-VEGF agents in the ocular anterior chamber has been proposed for the treatment of neovascular glaucoma and potential side effects on the corneal structures have been investigated with contrasting results. Increasing evidence has demonstrated that VEGF inhibition is associated with cellular apoptotic changes and that this effect may be mediated by alterations in nerve growth factor (NGF) pathway.

The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS Activation.

Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD.