Role of SOCS and VHL Proteins in Neuronal Differentiation and Development.

The basic helix-loop-helix factors play a central role in neuronal differentiation and nervous system development, which involve the Notch and signal transducer and activator of transcription (STAT)/small mother against decapentaplegic signaling pathways. Neural stem cells differentiate into three nervous system lineages, and the suppressor of cytokine signaling (SOCS) and von Hippel-Lindau (VHL) proteins are involved in this neuronal differentiation. The SOCS and VHL proteins both contain homologous structures comprising the BC-box motif.

SOCS7-Derived BC-Box Motif Peptide Mediated Cholinergic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells.

Adipose-derived mesenchymal stem cells (ADMSCs) are a type of pluripotent somatic stem cells that differentiate into various cell types such as osteoblast, chondrocyte, and neuronal cells. ADMSCs as donor cells are used to produce regenerative medicines at hospitals and clinics. However, it has not been reported that ADMSCs were differentiated to a specific type of neuron with a peptide.

BC-Box Motif in SOCS6 Induces Differentiation of Epidermal Stem Cells into GABAnergic Neurons.

The BC-box motif in suppressor of cytokine signaling 6 (SOCS6) promotes the neuronal differentiation of somatic stem cells, including epidermal stem cells. SOCS6 protein belongs to the group of SOCS proteins and inhibits cytokine signaling. Here we showed that epidermal stem cells were induced to differentiate into GABAnergic neurons by the intracellular delivery of a peptide composed of the amino-acid sequences encoded by the BC-box motif in SOCS6 protein.

Role of VHL-JAK-STAT signaling pathway in central nervous system hemangioblastoma associated with von Hippel-Lindau disease.

Introduction: Central nervous system hemangioblastoma is a benign tumor associated with or without von Hippel-Lindau (VHL) disease which is an autosomal dominant hereditary disease that results from a germline mutation in the VHL gene. A main axis of signaling pathways in central nervous system hemangioblastoma is VHL-HIF signaling pathway. Here, we propose an alternative VHL-JAK-STAT signaling pathway in hemangioblastoma and discuss the role.

BC-Box Motif-Mediated Neuronal Differentiation of Somatic Stem Cells.

Von Hippel-Lindau tumor suppressor protein (pVHL) functions to induce neuronal differentiation of neural stem/progenitor cells (NSCs) and skin-derived precursors (SKPs). Here we identified a neuronal differentiation domain (NDD) in pVHL. Neuronal differentiation of SKPs was induced by intracellular delivery of a peptide composed of the amino-acid sequences encoded by the NDD.

[Benefit of Intraoperative Mannitol Use during Endoscopic Surgery for Intracerebral Hemorrhage].

Background: Endoscopic hematoma evacuation is an established treatment option for patients with intra- cerebral hemorrhage (ICH). The purpose of this study is to investigate the benefit of mannitol use during en- doscopic hematoma evacuation.

Methods: One hundred patients with ICH treated by endoscopic surgery from June 2009 to November 2014 were retrospectively reviewed.

Intrasellar Symptomatic Salivary Gland Rest with Inflammations.

Background: Instances of ectopic salivary gland tissue within the pituitary gland are rare, they are mostly asymptomatic, and the underlying pathophysiology of symptomatic cases is unclear. We report a case of intrasellar salivary gland rest that presented clinical symptoms and clearly related to inflammatory changes.

Case Description: In the present case, headache, bitemporal hemianopia, and hormone abnormality led to the detection of ectopic salivary gland tissue within the pituitary gland of a 24-year-old man.

Isolation of multipotent nestin-expressing stem cells derived from the epidermis of elderly humans and TAT-VHL peptide-mediated neuronal differentiation of these cells.

A specialized population of cells residing in the hair follicle is quiescent but shows pluripotency for differentiating into epithelial-mesenchymal lineage cells. Therefore, such cells are hoped to be useful as implantable donor cells for regenerative therapy. Recently, it was reported that intracellular delivery of TAT-VHL peptide induces neuronal differentiation of skin-derived precursors.

Skin-derived precursors differentiating into dopaminergic neuronal cells in the brains of Parkinson disease model rats.

Object: In the authors' previous study, they observed that amino acids 157-171 of von Hippel-Lindau protein (VHL peptide) induced neuronal differentiation of skin-derived precursors. They also noted that transplantation of these differentiated cells into the striata of a Parkinson disease (PD) rat model reduced apomorphine-induced rotations. In the present study, they investigated if these cells produce dopamine in the striatum.

Engrafted VHL peptide-delivered bone marrow stromal cells promote spinal cord repair in rats.

Stem cell-based therapy using bone marrow stromal cells (MSCs) has been expected to be a promising therapy for neuronal regeneration. To repair the injured spinal cord, neuronal differentiation of MSCs before transplantation has a more satisfactory effect. Recently, neuronal differentiation of neural progenitor/stem cells by an intracellular delivery of a pVHL-derived synthetic peptide (VHL peptide) has been shown.

Neuronal differentiation of neural progenitor cells by intracellular delivery of synthetic oligopeptide derived from Von Hippel-Lindau protein.

Intracellular delivery of synthetic oligopeptides has the potential to promote the occurrence of various cellular events such as cell death, proliferation, growth inhibition, metabolic changes, and morphological changes. However, the regulation of cellular differentiation by intracellular delivery of synthetic oligopeptides has been little studied. Von Hippel-Lindau protein (pVHL) is one of the proteins that functions to induce the differentiation of neural progenitor cells (NPCs).

Transplantation of Von Hippel-Lindau peptide delivered neural stem cells promotes recovery in the injured rat spinal cord.

For transplantation of neural stem cells (NSCs) to repair the injured spinal cord, neuronal differentiation of NSCs before transplantation has more satisfactory effect because differentiation grafted NSCs are restricted to the glial lineage. Therefore, we focused on the Von Hippel-Lindau protein (VHL), which has the potential to induce neuronal differentiation of NSCs. Here, we show the transplantation of protein transduction domain-linked VHL peptide-delivered NSCs promotes the repair of the injured spinal cord.

Efficient generation of dopamine neuron-like cells from skin-derived precursors with a synthetic peptide derived from von Hippel-Lindau protein.

Skin-derived precursors (SKPs) from mammalian dermis represent neural crest-related stem cells capable of differentiating into both neural and mesodermal progency. SKPs are of clinical interest because they serve as accessible autologous donor cells for neuronal repair for neuronal intractable diseases. However, little is known about the efficient generation of neurons from SKPs, and phenotypes of neurons generated from SKPs have been restricted.

Transethmoidal meningoencephalocele in an elderly woman. Case report.

A 69-year-old woman presented with a transethmoidal meningoencephalocele manifesting as gradually developing anosmia. Examinations revealed a mass in the nasal cavity associated with multiple angiomas in her lip and orbit. Neuroimaging showed meningoencephalocele extending via the ethmoid sinus to the nasal cavity.

The role of von Hippel-Lindau protein in the differentiation of neural progenitor cells under normoxic and anoxic conditions.

Von Hippel-Lindau protein (pVHL) normally functions to cause ubiquitin-mediated degradation of hypoxia-inducible factor-1alpha (HIF-1alpha) under normoxic but not under hypoxic conditions, and induces neuronal differentiation of neural progenitor cells. However, the role of pVHL in the differentiation of neural progenitor cells under either condition has not been fully elucidated. Herein, we show that under the anoxic condition the expression of pVHL and neuronal markers in neural progenitor cells was inhibited, while HIF-1alpha was induced.