Long-term efficacy of intrathecal cyclodextrin in patients with Niemann-Pick disease type C
Niemann –Pick type C (NPC) is a rare lysosomal storage disease characterized by hepatosplenomegaly and progressive neurological deterioration due to abnormal intracellular cholesterol transport. Cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (HPBCD) is an effective treatment for NPC; however, few reports have shown its long-term efficacy and safety. To demonstrate long-term efficacy and safety of intrathecal HPBCD (IT-HPBCD) treatment for NPC, we herein reports five patients with NPC treated using IT-HPBCD for 4–11 years. (Source: Brain and Development)
Source: Brain and Development - March 6, 2024 Category: Neurology Authors: Muneaki Matsuo, Takafumi Sakakibara, Yoshio Sakiyama, Tetsumin So, Motomichi Kosuga, Toshihiko Kakiuchi, Fumio Ichinose, Takuji Nakamura, Yoichi Ishitsuka, Tetsumi Irie Tags: Original Article Source Type: research
Repositioning of ezetimibe for the treatment of idiopathic pulmonary fibrosis
In conclusion, our study presents ezetimibe as a potential novel therapeutic for idiopathic pulmonary fibrosis.PMID:38359963 | DOI:10.1183/13993003.00580-2023 (Source: Respiratory Care)
Source: Respiratory Care - February 15, 2024 Category: Respiratory Medicine Authors: Chanho Lee Se Hyun Hyun Jisu Han Ju Hye Shin Byunghun Yoo Yu Seol Lee Jeong Su Park Beom Jin Lim Jin Gu Lee Young Sam Kim Song Yee Kim Soo Han Bae Source Type: research
Can NPC1L1 inhibitors reduce the risk of biliary tract cancer? Evidence from a mendelian randomization study
Oxysterols have been implicated in biliary tract cancer (BTC), and Niemann-Pick C1 –like 1 (NPC1L1) has been associated with oxysterol uptake in biliary and intestinal cells. Thus, our study aims to investigate the potential causal link between genetically proxied NPC1L1 inhibitors and the risk of BTC. (Source: Digestive and Liver Disease)
Source: Digestive and Liver Disease - February 10, 2024 Category: Gastroenterology Authors: Hao Dong, Rong Chen, Jiafeng Wang, Ningli Chai, Enqiang Linghu Tags: Oncology Source Type: research
Novel compound heterozygous mutations of the NPC1 gene associated with Niemann-pick disease type C: a case report and review of the literature
Niemann-Pick Disease type C is a fatal autosomal recessive lipid storage disorder caused by NPC1 or NPC2 gene mutations and characterized by progressive, disabling neurological deterioration and hepatosplenomegal... (Source: BMC Infectious Diseases)
Source: BMC Infectious Diseases - January 30, 2024 Category: Infectious Diseases Authors: Chaoxin Tao, Min Zhao, Xiaohui Zhang, Jihong Hao, Qiuyue Huo, Jie Sun, Jiangtao Xing, Yuna Zhang, Jianhong Zhao and Huaipeng Huang Tags: Case Report Source Type: research
NPC1L1 rs217434 A & gt; G as a Novel Single Nucleotide Polymorphism Related to Dyslipidemia in a Korean Population
This study provided evidence for a relationship between the NPC1L1 rs217434 A > G genotype and dyslipidemia in the Korean population, which highlights the potential of the NPC1L1 rs217434 A > G genotype as an early predictor of dyslipidemia.PMID:38280151 | DOI:10.1007/s10528-023-10649-6 (Source: Biochemical Genetics)
Source: Biochemical Genetics - January 27, 2024 Category: Genetics & Stem Cells Authors: Dahyun Cho Ximei Huang Youngmin Han Minjoo Kim Source Type: research
Increased rigidity and bioisosteric replacement in the design, synthesis and preliminary evaluation of novel, functionalized 3,3-dialkyl- γ-butyrolactones as sigma-2 ligands
AbstractThe sigma-2 ( σ2) receptor has been linked to several diseases and conditions including cancer, neuropathic drug addiction, Alzheimer ’s disease, Parkinson’s disease, traumatic brain injury, Niemann-Pick disease, schizophrenia, depression, and anxiety. Targeting σ2 as a means of treating these diseases and conditions has been the subject of intense research, and several clinical trials have been launched to determine the real-world therapeutic utility of this target. Herein, we report the identification of a novel, semirigid series of functionalized 3,3-dialkyl- γ-butyrolactone σ2 ligands, containing pipera...
Source: Medicinal Chemistry Research - January 27, 2024 Category: Chemistry Source Type: research
Association of NPC1L1 and HMGCR gene polymorphisms with coronary artery calcification in patients with premature triple-vessel coronary disease
Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. Niemann-Pick C1-like 1 (NPC1L1) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are the therapeutic targets of ez... (Source: BMC Medical Genomics)
Source: BMC Medical Genomics - January 17, 2024 Category: Genetics & Stem Cells Authors: Yulong Li, Jiawen Li, Xiaofang Tang, Jingjing Xu, Ru Liu, Lin Jiang, Jian Tian, Yin Zhang, Dong Wang, Kai Sun, Bo Xu, Wei Zhao, Rutai Hui, Runlin Gao, Lei Song, Jinqing Yuan & hellip; Tags: Research Source Type: research
GSE252944 Cholesterol biosynthesis inhibition synergizes with AKT inhibitors in triple-negative breast cancer
Contributors : Alissandra Hillis ; Alex Toker ; Ralitsa MadsenSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensTriple-negative breast cancer (TNBC) is responsible for a disproportionate number of breast cancer deaths due to its molecular heterogeneity, high recurrence rate and lack of targeted therapies. Dysregulation of the phosphoinositide 3-kinase (PI3K)/AKT pathway occurs in approximately 50% of TNBC patients. We performed a genome-wide negative selection CRISPR/Cas9 screen with PI3K and AKT inhibitors to identify targetable synthetic lethalities in TNBC. We found that chole...
Source: GEO: Gene Expression Omnibus - January 14, 2024 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
The paracaspase MALT1 controls cholesterol homeostasis in glioblastoma stem-like cells through lysosome proteome shaping
Cell Rep. 2024 Jan 5;43(1):113631. doi: 10.1016/j.celrep.2023.113631. Online ahead of print.ABSTRACTGlioblastoma stem-like cells (GSCs) compose a tumor-initiating and -propagating population remarkably vulnerable to variation in the stability and integrity of the lysosomal compartment. Previous work has shown that the expression and activity of the paracaspase MALT1 control GSC viability via lysosome abundance. However, the underlying mechanisms remain elusive. By combining RNA sequencing (RNA-seq) with proteome-wide label-free quantification, we now report that MALT1 repression in patient-derived GSCs alters the homeostas...
Source: Cancer Control - January 6, 2024 Category: Cancer & Oncology Authors: Cl ément Maghe Kilian Trillet Gwennan Andr é-Grégoire Mathilde Kerherv é Laura Merlet Kathryn A Jacobs Kristine Schauer Nicolas Bid ère Julie Gavard Source Type: research
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
We report that the degradation of targets such as splenocytes and erythrocytes by phagolysosomes occurs in a stepwise fashion, requiring lysis of their plasmalemmal bilayer as an essential initial step. This is achieved by the direct extraction of cholesterol facilitated by Niemann-Pick protein type C2 (NPC2), which in turn hands off cholesterol to NPC1 for export from the phagolysosome. The removal of cholesterol ulimately destabilizes and permeabilizes the membrane of the phagocytic target, allowing access of hydrolases to its internal compartments. In contrast, we found that saposins, which activate the hydrolysis of sp...
Source: European Journal of Cell Biology - January 3, 2024 Category: Cytology Authors: Dante Barreda Sergio Grinstein Spencer A Freeman Source Type: research
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
We report that the degradation of targets such as splenocytes and erythrocytes by phagolysosomes occurs in a stepwise fashion, requiring lysis of their plasmalemmal bilayer as an essential initial step. This is achieved by the direct extraction of cholesterol facilitated by Niemann-Pick protein type C2 (NPC2), which in turn hands off cholesterol to NPC1 for export from the phagolysosome. The removal of cholesterol ulimately destabilizes and permeabilizes the membrane of the phagocytic target, allowing access of hydrolases to its internal compartments. In contrast, we found that saposins, which activate the hydrolysis of sp...
Source: European Journal of Cell Biology - January 3, 2024 Category: Cytology Authors: Dante Barreda Sergio Grinstein Spencer A Freeman Source Type: research
Target lysis by cholesterol extraction is a rate limiting step in the resolution of phagolysosomes
We report that the degradation of targets such as splenocytes and erythrocytes by phagolysosomes occurs in a stepwise fashion, requiring lysis of their plasmalemmal bilayer as an essential initial step. This is achieved by the direct extraction of cholesterol facilitated by Niemann-Pick protein type C2 (NPC2), which in turn hands off cholesterol to NPC1 for export from the phagolysosome. The removal of cholesterol ulimately destabilizes and permeabilizes the membrane of the phagocytic target, allowing access of hydrolases to its internal compartments. In contrast, we found that saposins, which activate the hydrolysis of sp...
Source: European Journal of Cell Biology - January 3, 2024 Category: Cytology Authors: Dante Barreda Sergio Grinstein Spencer A Freeman Source Type: research
Increased rigidity and bioisosteric replacement in the design, synthesis and preliminary evaluation of novel, functionalized 3,3-dialkyl- γ-butyrolactones as sigma-2 ligands
AbstractThe sigma-2 ( σ2) receptor has been linked to several diseases and conditions including cancer, neuropathic drug addiction, Alzheimer ’s disease, Parkinson’s disease, traumatic brain injury, Niemann-Pick disease, schizophrenia, depression, and anxiety. Targeting σ2 as a means of treating these diseases and conditions has been the subject of intense research, and several clinical trials have been launched to determine the real-world therapeutic utility of this target. Herein, we report the identification of a novel, semirigid series of functionalized 3,3-dialkyl- γ-butyrolactone σ2 ligands, containing pipera...
Source: Medicinal Chemistry Research - December 29, 2023 Category: Chemistry Source Type: research
Expert commentary for: Late adult-onset Niemann Pick type C (NPC): An “atypical” typical presentation at the age of 62
In a recently Movement Disorders Rounds, Dr. Mario Sousa and colleagues describe a challenging case of a late onset Niemann Pick Type C (NPC) disease [1]. The patient was a 67-year-old woman that started at the age of 62 with a progressive gait and balance disorder, cognitive impairment and speech affection. Summarizing main findings in neurological examination the patient presented a vertical supra-nuclear gaze palsy (VSGP) in combination with a mild cerebellar ataxia, slight slowness without decreasing of amplitude in finger tapping test, absence of rigidity and a wide based gait. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - December 28, 2023 Category: Neurology Authors: S. Rodriguez-Quiroga Source Type: research
Late adult-onset Niemann Pick type C (NPC): An “atypical” typical presentation at the age of 62. Expert commentary
In a recently Movement Disorders Rounds, Dr. Mario Sousa and colleagues describe a challenging case of a late onset Niemann Pick Type C (NPC) disease [1]. The patient was a 67-year-old woman that started at the age of 62 with a progressive gait and balance disorder, cognitive impairment and speech affection. Summarizing main findings in neurological examination the patient presented a vertical supra-nuclear gaze palsy (VSGP) in combination with a mild cerebellar ataxia, slight slowness without decreasing of amplitude in finger tapping test, absence of rigidity and a wide based gait. (Source: Parkinsonism and Related Disorders)
Source: Parkinsonism and Related Disorders - December 28, 2023 Category: Neurology Authors: Sergio Rodriguez-Quiroga Source Type: research
