Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse

  title={Decreased expression of myelin gene regulatory factor in Niemann-Pick type C 1 mouse},
  author={Xin Yan and Jan Lukas and Martin Witt and Andreas Wree and Rayk H{\"u}bner and Moritz J. Frech and R{\"u}diger K{\"o}hling and Arndt Rolfs and Jiankai Luo},
  journal={Metabolic Brain Disease},
Niemann-Pick type C 1 (NPC1) disease is an autosomal recessive cholesterol transport defect resulting in a neurodegenerative process in patients mainly at an early age, although some patients may start with manifestation in adult. Since loss of myelin is considered as a main pathogenetic factor, the precise mechanism inducing dysmylination in NPC1 disease is still unclear. In the present study, a quantitative evaluation on the myelin protein and its regulatory factors of oligodendrocytes, such… 

Altered myelination in the Niemann-Pick type C1 mutant mouse.

It is demonstrated that mutation of the Npc1 gene is sufficient to cause severe and progressive defects in myelination in the mouse brain and the expression of myelin genes and proteins is strongly inhibited from postnatal day 35 onwards including reduced myelin basic protein (MBP) expression in the brain.

Lovastatin promotes myelin formation in NPC1 mutant oligodendrocytes

Olfactory Deficits in Niemann-Pick Type C1 (NPC1) Disease

A pronounced neurodegeneration and glia activation in the olfactory system of NPC1−/− animals is demonstrated, accompanied by sensory deficits, which underlines the critical role and location of the OB as a possible entrance gate for noxious substances.

Myelin Defects in Niemann–Pick Type C Disease: Mechanisms and Possible Therapeutic Perspectives

This review will focus on myelin defects and the pivotal importance of cholesterol for myelination and will offer an overview of the molecular targets and the pharmacological strategies so far proposed, or an object of clinical trials for NPC.

npc2-Deficient Zebrafish Reproduce Neurological and Inflammatory Symptoms of Niemann-Pick Type C Disease

The present study generated and characterized a zebrafish mutant that lacks Npc2 protein that may be useful for studies at the organismal, cellular, and molecular levels and both small-scale and high-throughput screens.

Hyperactive glial cells contribute to axonal pathologies in the spinal cord of Npc1 mutant mice

The data suggest that the axonal pathologies in the Npc1 mutant spinal cord are strongly correlated with the increase of activated glial cells, which produce IL‐1β and ApoE, resulting in the activation of p38‐MAPK signaling pathway and enhanced phosphorylated tau protein.

Defects in the retina of Niemann-pick type C 1 mutant mice

The authors' data extend previous findings to show multiple defects in the retina of Npc1 mutant mice, suggesting an important role of NPC1 protein in the normal function of the retina.

Increased Regenerative Capacity of the Olfactory Epithelium in Niemann–Pick Disease Type C1

Olfactory testing may provide useful information to monitor pharmacologic treatment approaches in human NPC1 and observed considerable loss of mature olfactory receptor neurons as well as an increased number of proliferating and apoptotic cells after both therapy approaches.

Developmental delay in motor skill acquisition in Niemann-Pick C1 mice reveals abnormal cerebellar morphogenesis

These findings indicate that in Npc1nmf164 homozygous mice the derangement of synaptic connectivity and dysmyelination during cerebellar morphogenesis largely anticipate motor deficits that are typically observed during adulthood.

Electrodiagnostic testing and histopathologic changes confirm peripheral nervous system myelin abnormalities in the feline model of niemann-pick disease type C.

There was a shift to small myelinated fibers in affected cats, and there were significant decreases in fiber diameter, axon diameter, and myelin thickness, similar to those described in the murine NPC disease model and in rare patients in whom nerve biopsy has been performed.



Perturbed Myelination Process of Premyelinating Oligodendrocyte in Niemann‐PickType C Mouse

In hypomyelinated white matter, strong immunoreactivity of polysialylated-neural cell adhesion molecule, a negative regulator of myelination, was observed in axons.

Molecular, anatomical, and biochemical events associated with neurodegeneration in mice with Niemann-Pick type C disease.

These studies show there is a compensatory increase in NPC2 and LipA in an attempt to overcome the physiological defect caused by the mutation, and neurodegeneration proceeds utilizing apoptosis with activation of glial cells, increased apoE and apoD synthesis, and increased cholesterol turnover across the CNS.

Patterned Purkinje cell degeneration in mouse models of Niemann‐Pick type C disease

Investigation of Purkinje cell death in two murine models of NPC1, BALB/c npcnih and C57BLKS/J spm finds pattern of cell death reflects the fundamental compartmentation of the cerebellum into zones and stripes.

Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.

Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking.

Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.

The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.

Identification of HE1 as the second gene of Niemann-Pick C disease.

Treatment of NP-C2 fibroblasts with exogenous recombinant HE1 protein ameliorated lysosomal accumulation of low density lipoprotein-derived cholesterol.

[Niemann-Pick disease type C].

Niemann-Pick disease type C is an autosomal recessive neurovisceral lipid storage disorder, but the basic defect has not yet been clarified, and many therapies, i.e. dimethyl sulfoxide, low-cholesterol diet and transplantations, have been challenged but improvement of neurological symptoms have not been reported.

Sox10, a Novel Transcriptional Modulator in Glial Cells

A role for Sox10 is proposed in conferring cell specificity to the function of other transcription factors in developing and mature glia, including Pax3 and Krox-20, twoother transcription factors involved in Schwann cell development.