1,721,166 research outputs found
From genes to pain: nerve growth factor and hereditary sensory and autonomic neuropathy type V
No full textHereditary sensory and autonomic neuropathy type V (HSAN V) is an autosomal recessive disorder characterized by the loss of deep pain perception. The anomalous pain and temperature sensations are due to the absence of nociceptive sensory innervation. The neurotrophin nerve growth factor (NGF), by binding to tropomyosin receptor A (TrkA) and p75NTR receptors, is essential for the development and survival of sensory neurons, and for pain perception during adulthood. Recently a homozygous missense mutation (R100W) in the NGF gene has been identified in HSAN V patients. Interestingly, alterations in NGF signalling, due to mutations in the NGF TRKA gene, have also been involved in another congenital insensitivity to pain, HSAN IV, characterized not only by absence of reaction to painful stimuli, but also anhidrosis and mental retardation. These symptoms are absent in HSAN V patients. Unravelling the mechanisms that underlie the differences between HSAN IV and V could assist in better understanding NGF biology. This review highlights the recent key findings in the understanding of HSAN V, including insights into the molecular mechanisms of the disease, derived from genetic studies of patients with this disorder
Getting into the brain: the intranasal approach to enhance the delivery of nerve growth factor and its painless derivative in Alzheimer's disease and down syndrome
Full text linkThe neurotrophin Nerve Growth Factor (NGF) holds a great potential as a therapeutic candidate for the treatment of neurological diseases. However, its safe and effective delivery to the brain is limited by the fact that NGF needs to be selectively targeted to the brain, to avoid severe side effects such as pain and to bypass the blood brain barrier. In this perspective, we will summarize the different approaches that have been used, or are currently applied, to deliver NGF to the brain, during preclinical and clinical trials to develop NGF as a therapeutic drug for Alzheimer's disease. We will focus on the intranasal delivery of NGF, an approach that is used to deliver proteins to the brain in a non-invasive, safe, and effective manner minimizing systemic exposure. We will also describe the main experimental facts related to the effective intranasal delivery of a mutant form of NGF [painless NGF, human nerve growth factor painless (hNGFp)] in mouse models of Alzheimer's disease and compare it to other ways to deliver NGF to the brain. We will also report new data on the application of intranasal delivery of hNGFp in Down Syndrome mouse model. These new data extend the therapeutic potential of hNGFp for the treatment of the dementia that is progressively associated to Down Syndrome. In conclusion, we will show how this approach can be a promising strategy and a potential solution for other unmet medical needs of safely and effectively delivering this neuroprotective neurotrophin to the brain
Inhibitor of astrocyte TNF alpha for use in the treatment of neurological diseases
No full textHuman NGF form comprising two mutations, a first mutation being represented by the substitution of the proline amino acid 61 with serine, a second mutation being represented by the substitution of an aminoacid in any of the positions 95-101, for the simultaneous use as agent for the activation of the chemokine SDF-1alpha and as an agent for the inhibition of the activity of the cytokine TNF alph
Design and characterization of human Nerve Grwoth Factor muteins with reduced algesic properties and their application to drug discovery in Alzheimer's disease
No full textNON HUMAN TRANSGENIC ANIMAL AS A MODEL OF NEURODEGENERATIVE DISEASES AND FOR THE EARLY DIAGNOSIS THEREOF
No full textINIBITORE DI TNF ALPHA ASTROCITARIO PER L’USO NEL TRATTAMENTO DI MALATTIE NEUROLOGICHE
No full textForma mutata umana di NGF comprendente due mutazioni, una prima mutazione essendo rappresentata dalla sostituzione dell’aminoacido prolina in posizione 61 con una serina, una seconda mutazione essendo rappresentata dalla sostituzione di un aminoacido in una qualsiasi delle posizioni 95-101, per uso simultaneo come agente per l’attivazione della chemochina SDF 1alpha e come agente per l’inibizione dell’attività della citochina TNF alph
Cholinesterase inhibitors with a nicotinic mode of action: Neuroprotection in anti-NGF mice
No full textDesign and characterization of human Nerve Growth Factor muteins with reduced algesic properties and their application to drug discovery in Alzheimer’s disease
No full textTransgenic mouse models of neurotrophin function and effects on amyloid plaques and neurofibrillary pathology
No full text- …
