Mammalian Diaphanous1 signalling in neurovascular complications of diabetes.

Over the past few decades, diabetes gradually has become one of the top non-communicable disorders, affecting 476.0 million in 2017 and is predicted to reach 570.9 million people in 2025.

New insights into RAGE/Diaph1 interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system in long-term hyperglycaemia.

This review focuses on receptor for advanced glycation endproducts/diaphonous related formin 1 (RAGE/Diaph1) interaction as a modulator of actin cytoskeleton dynamics in peripheral nervous system (PNS) in diabetes. Deciphering the complex molecular interactions between RAGE and Diaph1 is crucial in expanding our understanding of diabetic length dependent neuropathy (DLDN). DLDN is a common neurological disorder in patients with diabetes.

The receptor for advanced glycation end products and its ligands' expression in OVE26 diabetic sciatic nerve during the development of length-dependent neuropathy.

Type 1 diabetes (T1D) may affect the peripheral nervous system and alter the expression of proteins contributing to inflammation and cellular cytoskeleton dysfunction, in most cases leading to the development of diabetic length-dependent neuropathy (DLDN). In the present study, we performed immunohistochemistry (IHC) to probe the expression of the receptor for advanced glycation end products (RAGE); its key ligands, high-mobility group box 1 (HMGB1), S100 calcium-binding protein B (S100B), and carboxymethyl-lysine (CML - advanced glycation end products (AGE)); and its cytoplasmic tail-binding partner, diaphanous related formin 1 (DIAPH1) and associated molecules, beta-actin (ACTB) and profilin 1 (PFN1) proteins in sciatic nerves harvested from seven-month old FVB/OVE26 mice with genetically-mediated T1D. We found that the amount of RAGE, HMGB1, and S100B proteins was elevated in diabetic vs the non-diabetic groups, while the amount of DIAPH1, ACTB, as well as PFN1 proteins did not differ between these groups.

Peripheral Neuropathy Presents Similar Symptoms and Pathological Changes in Both High-Fat Diet and Pharmacologically Induced Pre- and Diabetic Mouse Models.

The objective of the study was to compare the effects of experimentally induced type 1 or type 2 diabetes (T1D or T2D) on the functional, structural and biochemical properties of mouse peripheral nerves. Eight-week-old C57BL/6 mice were randomly assigned into three groups, including the control (CTRL, chow-fed), STZ (streptozotocin (STZ)-injected), and HFD (high-fat diet (HFD)-fed) group. After 18-weeks of experimental treatment, HFD mice had higher body weights and elevated levels of plasma lipids, while STZ mice developed hyperglycemia.

Risk Factors and Emerging Therapies in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by a permanent degeneration of both upper and lower motor neurons. Many different genes and pathophysiological processes contribute to this disease, however its exact cause remains unclear. Therefore, it is necessary to understand this heterogeneity to find effective treatments.

The Receptor for Advanced Glycation End Products (RAGE) and DIAPH1: Implications for vascular and neuroinflammatory dysfunction in disorders of the central nervous system.

The Receptor for Advanced Glycation End Products (RAGE) is expressed by multiple cell types in the brain and spinal cord that are linked to the pathogenesis of neurovascular and neurodegenerative disorders, including neurons, glia (microglia and astrocytes) and vascular cells (endothelial cells, smooth muscle cells and pericytes). Mounting structural and functional evidence implicates the interaction of the RAGE cytoplasmic domain with the formin, Diaphanous1 (DIAPH1), as the key cytoplasmic hub for RAGE ligand-mediated activation of cellular signaling. In aging and diabetes, the ligands of the receptor abound, both in the central nervous system (CNS) and in the periphery.

Chemotherapy-induced neuropathies-a growing problem for patients and health care providers.

Introduction: Chemotherapy-induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti-cancer drugs are: platinum-based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.

Soluble RAGE Treatment Delays Progression of Amyotrophic Lateral Sclerosis in SOD1 Mice.

The etiology of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disorder characterized by progressive muscle weakness and spasticity, remains largely unknown. Approximately 5-10% of cases are familial, and of those, 15-20% are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). Mutations of the SOD1 gene interrupt cellular homeostasis and contribute to cellular toxicity evoked by the presence of altered SOD1, along with other toxic species, such as advanced glycation end products (AGEs).

Receptor for Advanced Glycation End Products and its Inflammatory Ligands are Upregulated in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder of largely unknown pathogenesis. Recent studies suggest that enhanced oxidative stress and neuroinflammation contribute to the progression of the disease. Mounting evidence implicates the receptor for advanced glycation end-products (RAGE) as a significant contributor to the pathogenesis of certain neurodegenerative diseases and chronic conditions.

RAGE axis in neuroinflammation, neurodegeneration and its emerging role in the pathogenesis of amyotrophic lateral sclerosis.

RAGE, the receptor of advanced glycation end-products, is thought to be one of the potential contributors to the neurodegeneration. It has been shown that RAGE activation triggers an increase in proinflammatory molecules, oxidative stressors and cytokines. RAGE involvement has been documented in the pathogenesis of a number of neurodegenerative diseases such amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, Creutzfeld-Jakob' diseases and various neurodegenerative conditions such as diabetic neuropathy, familial amyloid polyneuropathy, Charcot neuroarthropathy and vasculitic neuropathy.

Origins and neurochemical complexity of preganglionic neurons supplying the superior cervical ganglion in the domestic pig.

The superior cervical ganglion (SCG) is a center of sympathetic innervation of all head and neck organs. SCG sympathetic preganglionic neurons (SPN) were found in the nucleus intermediolateralis pars principalis (IMLpp), the nucleus intermediolateralis pars funicularis (IMLpf), the nucleus intercalatus spinalis (IC), and the nucleus intercalatus spinalis pars paraependymalis (ICpe). Despite its importance, little is known of SCG innervation and chemical coding in the laboratory pig, a model that is physiologically and anatomically representative of humans.

Increased expression of the receptor for advanced glycation end-products in human peripheral neuropathies.

Background: Diabetic neuropathy and idiopathic neuropathy are among the most prevalent neuropathies in human patients. The molecular mechanism underlying pathological changes observed in the affected nerve remains unclear but one candidate molecule, the receptor for advanced glycation end-products (RAGE), has recently gained attention as a potential contributor to neuropathy. Our previous studies revealed that RAGE expression is higher in porcine and murine diabetic nerve, contributing to the inflammatory mechanisms leading to diabetic neuropathy.

Impaired slow axonal transport in diabetic peripheral nerve is independent of RAGE.

Diabetic peripheral nerve dysfunction is a common complication occurring in 30-50% of long-term diabetic patients. The pathogenesis of this dysfunction remains unclear but growing evidence suggests that it might be attributed, in part, to alteration in axonal transport. Our previous studies demonstrated that RAGE (Receptor for Advanced Glycation Endproducts) contributes to the pathogenesis of diabetic peripheral neuropathy and impairs nerve regeneration consequent to sciatic nerve crush, particularly in diabetes.

Reduced expression of Munc13-1 in human and porcine diabetic peripheral nerve.

Peripheral neuropathy (PN) involves widespread peripheral nerve disorders affecting a large human population worldwide. In Europe and the United States, the first single most prominent cause of peripheral neuropathy is diabetes, affecting 60-70% patients with long-term diabetes followed by idiopathic neuropathy, peripheral nerve damage of unknown etiology, diagnosed in 10-40% of all patients admitted to hospitals with symptoms of peripheral nerve damage. The molecular mechanisms underlying the pathogenesis of this disorder are not yet fully understood, however a few potential molecular contributors, such as Munc13-1, have been recently suggested.

Active zone protein expression changes at the key stages of cerebellar cortex neurogenesis in the rat.

Signal transduction and neurotransmitter release in the vertebrate central nervous system are confined to the structurally complex presynaptic electron dense projections called "active zones." Although the nature of these projections remains a mystery, genetic and biochemical work has provided evidence for the active zone (AZ) associated proteins i.e.

RAGE deficiency improves postinjury sciatic nerve regeneration in type 1 diabetic mice.

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses.

Morphological Changes and Immunohistochemical Expression of RAGE and its Ligands in the Sciatic Nerve of Hyperglycemic Pig (Sus Scrofa).

The aim of our project was to study the effect of streptozotocin (STZ)-induced hyperglycemia on sciatic nerve morphology, blood plasma markers and immunohistochemical expression of RAGE (the Receptor for Advanced Glycation End-products), and its ligands-S100B and Carboxymethyl Lysine (CML)-advanced glycation endproduct (AGE) in the laboratory pig. Six months after STZ-injections, blood plasma measurements, morphometric analysis of sciatic nerve fiber density, immunofluorescent distribution of potential molecular neuropathy contributors, ELISA measurement of plasma AGE level and HPLC analysis of sciatic nerve levels of one of the pre-AGE and the glycolysis intermediate products-methyl-glyoxal (MG) were performed. The results of our study revealed that STZ-injected animals displayed elevated levels of plasma glucose, gamma glutamyl transferase (GGT) and triglycerides.

Immunohistochemical characterization of superior cervical ganglion neurons supplying porcine parotid salivary gland.

The main goal of our study was to investigate the chemical coding of the superior cervical ganglion (SCG) sympathetic neurons supplying the porcine parotid gland. Additionally, the chemical nature of the vicinal nerve fibers surrounding the parotid SCG perikarya was investigated. Fast blue (FB) retrograde tracing of the parotid gland and immunofluorescent labelling of SCG neurons were studied in juvenile female pigs.