Ricerc@Sapienza

Liver diseases are a major health concern and affect a large proportion of people worldwide. There are over 100 types of liver disorders, including cirrhosis, cholangiocarcinoma (CCA), hepatocellular carcinoma, and hepatitis. Despite the relevant number of people who are affected by liver diseases, and the increased awareness with regard to these disorders, the number of deaths corresponding to liver injury is expected to increase in the foreseeable future.

The involvement of neuro-inflammation has been demonstrated in asthma, allergic rhinitis (AR), conjunctivitis and atopic dermatitis. Allergic reaction is associated with local production and release of neuromediators such as Nerve Growth Factor (NGF), substance P and Calcitonine-gene related peptide. Patients with allergic diseases showed increased serum and local NGF levels during inflammation or after allergen challenge.

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.

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.

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. Neurotrophins have been demonstrated to be key tumor promoting signaling platforms.

Regenerative capability of the peripheral nervous system after injury is enhanced by Schwann cells (SCs) producing several growth factors. The clinical use of SCs in nerve regeneration strategies is hindered by the necessity of removing a healthy nerve to obtain the therapeutic cells. Adipose-derived stem cells (ASCs) can be chemically differentiated towards a SC-like phenotype (dASCs), and represent a promising alternative to SCs. Their physiology can be further modulated pharmacologically by targeting receptors for neurotransmitters such as acetylcholine (ACh).

Muscarinic receptor activation modulates neurotrophic factors production in rat Schwann-like cells derived from adipose mesenchymal stem cells

Piovesana R1, Faroni A2, Soligo M3, Manni L3, Reid AJ2 & Tata AM1

Ethanol exposure during gestation is an early life stressor that profoundly dysregulates structure and functions of the embryonal nervous system, altering the cognitive and behavioral development. Such dysregulation is also achieved by epigenetic mechanisms, which, altering the chromatin structure, redraw the entire pattern of gene expression. In parallel, an oxidative stress response at the cellular level and a global upregulation of neuroendocrine stress response, regulated by the HPA axis, exist and persist in adulthood.

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.

The nerve growth factor (NGF) belongs to the family of neurotrophic factors. Initially discovered as a signaling molecule involved in the survival, protection, differentiation and proliferation of sympathetic and peripheral sensory neurons, it also participates in the regulation of the immune system and endocrine system. NGF biological activity is due to the binding of two classes of receptors: the tropomyosin-related kinase A (TrkA), and the low-affinity NGF pan-neurotrophin receptor p75.