Gene expression experiments with LDL receptor lacking primary FH fibroblasts, revealed that SR-BI and ABCA1 are important regulators for cholesterol acquisition in FH cells, consistent with findings in cells from NPC and TD patients.
These results indicate that the cholesterol trafficking defect in NPC disease results in reduced activity of ABCA1, which we suggest is responsible for the low HDL-cholesterol in the majority of NPC subjects and partially responsible for the overaccumulation of cellular lipids in this disorder.
In this study, we found that when ABCA1 is defective (Tangier disease) there is secondary inhibition of the NPC disease pathway, linking these two diseases at the level of cellular pathophysiology.
We previously reported that ABCA1 expression and HDL formation are impaired in the lysosomal cholesterol storage disorder Niemann-Pick disease type C1 and that plasma HDL-C is low in the majority of Niemann-Pick disease type C patients.
P-glycoprotein levels varied significantly among the various fibroblasts tested, but no correlation with NPC phenotype or rate of progesterone metabolism was noted, and P-glycoprotein inhibitors did not affect conversion of progesterone to products.
The Albumin-to-Alkaline Phosphatase Ratio (AAPR) has been recently revealed as a prognostic index for hepatocellular carcinoma, whereas its role in metastatic nasopharyngeal cancer (NPC) remains unclear.
We conclude that AnxA6 may participate in formation of cholesterol-rich platforms on LE and therefore may contribute to the pathology of the NPC disease.
This study aimed to detect the effect of EBV on Wnt inhibitory factor 1 (WIF1), Nemo-like kinase (NLK), and adenomatous polyposis coli (APC) gene methylation, and expression in gastric carcinoma and NPC.
For instance, apoD is overexpressed in neural tissues in Niemann-Pick's type C disease, after acute CNS injury and cerebral ischemia, Alzheimer's disease and by a number of different tumors such as breast, prostate, ovarian and endometrial carcinomas.
Niemann-Pick type C disease: accelerated neurofibrillary tangle formation and amyloid beta deposition associated with apolipoprotein E epsilon 4 homozygosity.
Increased CSF levels of Aβ(38), Aβ(40), and Aβ(42) and unaltered levels of β-cleaved soluble APP are consistent with increased γ-secretase-dependent Aβ release in the brains of patients with NPC.
Here, NPC1 null cells (CHO-NPC1-/-), exhibiting increased cholesterol levels and disturbed cholesterol transport similar to that observed in Niemann-Pick type C disease (NPC), were used to analyze the influence of altered cholesterol levels on APP-BACE1 proximity.
Collectively, our results reveal that overexpression of APP in Npc1-deficient mice can negatively influence longevity and a wide spectrum of behavioral/neuropathological abnormalities, thus raising the possibility that APP and NPC1 may interact functionally to regulate the development of AD and NPC pathologies.
We carried out genome-wide comparative transcriptome analyses of pre-symptomatic Npc1<sup>+/+</sup>/App<sup>+/+</sup>, Npc1<sup>-/-</sup>/App<sup>+/+</sup>, Npc1<sup>+/+</sup>/App<sup>-/-</sup>, and Npc1<sup>-/-</sup>/App<sup>-/-</sup> mouse cerebella to identify biological pathways in the NPC brain further affected by the loss of APP.
The pattern of Aβ peptides and sAPP-α/β fragments in cell media was differently affected by NPC-phenotype induced by U18666A treatment and by NPC1 ( -/- ) genotype.
Recent studies have shown that NPC disease exhibits intriguing parallels with Alzheimer's disease, including the presence of neurofibrillary tangles and increased levels of amyloid precursor protein (APP)-derived β-amyloid (Aβ) peptides in vulnerable brain neurons.
Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes.
Unregulated ARF6 activation attenuates the NPC phenotype at least in part by decreasing cholesterol accumulation and restoring normal sphingolipid trafficking.
Immunohistochemical analysis indicated that NPC patients with highly ARHGAP42 expression were significantly associated with shorter metastasis-free survival.
Although high expression of miR-BARTs has been detected in NPC patients, contributions of these more recently discovered viral products to the establishment of TME are still vaguely defined.
Taken together, our data demonstrate that downregulation of FoxM1 could improve the sensitivity of NPC cells to cisplatin through inhibition of MRN-ATM-mediated DNA repair, which could be related to FoxM1-dependent regulation of NBS1.[BMB Reports 2019; 52(3): 208-213].