Emerging Roles of Signal Transduction Pathways in Neurodegenerative Diseases. Hunting New Possible Therapeutic Molecular Targets

Illnesses following the degeneration of the nervous system can occur due to aging or genetic mutations and represent a clinical concern. In neurodegenerative diseases, loss of neuronal structure and functions mainly causes cognitive impairment, representing an increasing social burden. In neurodegenerative diseases, the progressive loss of vulnerable populations of neurons in specific regions of the central nervous system was traced to different pathological events, such as misfolded proteins’ accumulation, abnormalities in proteasomes or phagosomes, as well as anomalies in lysosomes or mitochondria. Many research efforts identified important events involved in neurodegeneration, but the complex pathogenesis of neurodegenerative diseases is far from being fully elucidated. More recently, insights into the signal transduction pathways acting in the nervous system contributed to unveiling some molecular mechanisms triggering neurodegeneration. Abnormalities in the intra- or inter-cellular signaling were described to be involved in the pathogenesis of neurodegenerative disease. Understanding the signal transduction pathways that impact the nervous system homeostasis can offer a wide panel of potential targets for modulating therapeutic approaches. The present review will discuss the main signal transduction pathways involved in neurodegenerative disorders

The Phosphoinositide Signal Transduction Pathway In Endometriosis: A Potential Prognostic And Therapeutic Tool

Uncontrolled calcium levels in the cell alter proteins function, apoptosis regulation, as well as proliferation, secretion and contraction. Calcium levels are tightly regulated by signal transduction pathways, including the Phosphoinositide (PI) system. A great interest was paid to PIs for their role in mammalian reproduction. Reports from the ‘80s indicated that the PI signal transduction pathway plays a role in the endocrine regulation of endometrium. PI-PLC enzymes were recently suggested to be involved in endometriosis. Recent studies demonstrated that the expression differed in normal endometrium with respect to endometriosis tissue. Remarkably, recent evidences indicated that PI-PLC isoforms might be involved in the inflammation cascade in different cytotypes. That suggests that PI-PLC enzymes might be related to the inflammatory cascade claimed in the pathogenesis of endometriosis

The Phosphoinositide signal transduction Pathway and the development of human nervous system

The development of nervous system is tightly regulated by a network of interconnected signal transduction pathways. The extensive crosstalk among different signal transduction systems deserves great attention. In fact, understanding the timing of the cascade of events regulating the development of the nervous system might open the way to novel therapeutic strategies. In the last 20 years, great interest was paid to the Phosphoinositide (PI) signal transduction pathway and related Phosphoinositide-specific phospholipids C (PI-PLC) family of converting enzymes, which contribute to the regulation of intracellular calcium levels. Beside their well-known role in the metabolism of calcium, PI-PLC enzymes interact with a number of molecules belonging to other signal transduction pathways, contributing to the peculiar and complex network in the developing nervous system. In the present communication, the connection of PI signalling and further transduction pathways acting during neural development will be analyzed, with special regard to the role of PI-PLC family of enzymes

The Phosphoinositide Signal Transduction Pathway In Endometriosis: A Potential Prognostic And Therapeutic Tool

Uncontrolled calcium levels in the cell alter proteins function, apoptosis regulation, as well as proliferation, secretion and contraction. Calcium levels are tightly regulated by signal transduction pathways, including the Phosphoinositide (PI) system. A great interest was paid to PIs for their role in mammalian reproduction. Reports from the ‘80s indicated that the PI signal transduction pathway plays a role in the endocrine regulation of endometrium. PI-PLC enzymes were recently suggested to be involved in endometriosis. Recent studies demonstrated that the expression differed in normal endometrium with respect to endometriosis tissue. Remarkably, recent evidences indicated that PI-PLC isoforms might be involved in the inflammation cascade in different cytotypes. That suggests that PI-PLC enzymes might be related to the inflammatory cascade claimed in the pathogenesis of endometriosis

Phosphoinositide Signal Transduction Pathway and Major Depression

Mood disorders, including major depression (MD), overall constitute a major medical need. In fact, mood disorders require chronic treatments, lathough not effective in all patients. Multiple deficits, including cell atrophy and loss, were described in limbic and cortical brain regions of patients affected with mood disorders and in experimental animal models. A number of changes in gene expression and activity was described in brains of mood disorder affected patients. Therapies act reciprocally regulating many of these changes. Antidepressant and mood stabilizing therapies restore these deficits by reestablishing proper patterns of gene expression and function. Different signal transduction pathways play a role in the pathogenesis of mood disorders, namely the cyclic‐AMP, phosphoinositides (PI), mitogen‐activated protein kinase, and glycogen synthase kinase cascades. Although significant progresses have been achieved in studying the signal transduction pathways possibly involved in mood disorders, their reciprocal interconnection and the effect of alterations in human brain, many issues remain to be addressed. Knowledge of these intriguing aspects might help to clarify the pathogenesis of MD, widening the panel of available therapeutic tools

1p36.32 rearrengements and the role of PI-PLC 2 in nervous tumours

Deletions in the distal region of the short arm of chromosome 1 (1p36) are widely diffuse, both in congenital 1p36 Deletion Syndrome and as somatic abnormalities in tumours. Rearrangements in 1p36 have been described in a broad spectrum of human neoplasias in addition to other chromosomal abnormalities. In neuroblastomas, wide hemizygous deletions in 1p36.23–1p36.32 have been described suggesting that the 1p36 region contains a tumour-suppressor gene involved in malignancy. A role for phosphoinositide (PI)-specific phospholipase C (PLC) ETA2, whose gene maps on 1p36.32, was suggested. PI-PLC ETA2 belongs to a family of enzymes related to the phosphoinositide signalling pathway, which provide an important intracellular signalling system involved in a variety of cell functions such as hormone secretion, neurotransmitter signal transduction, cell growth, membrane trafficking, ion channel activity, regulation of the cytoskeleton, cell cycle control and apoptosis. Expression of PI-PLC g2 occurs after birth and continues throughout the life. Synapse formation occurs during a short period of postnatal development. Thus, it is likely that PI-PLC ETA2 acts in formation and maintenance of the neuronal network in the brain. The fact that PI-PLC ETA2, a highly neuronspecific isozyme, is abundantly expressed in the postnatal brain suggests the importance of PI-PLC g2 in formation and maintenance of the neuronal network in the postnatal brain. Further studies are required to verify the possible involvement of PI-PLC ETA2 mutation/deletion in central nervous tumour tissues presenting abnormalities of the 1p36 chromosomal band