Niemann-Pick type C (NP-C) disease is a rare lysosomal storage disease caused by mutations in NPC1 (95% cases) or NPC2 (5% cases). (bvsalud.org)
Intracellular1
The NPC1 protein is involved in the intracellular lipid metabolism coordinating sterol trafficking. (biomedcentral.com)
Proteins2
Lysosomal storage diseases are inborn errors of metabolism that arise due to loss of function mutations in genes encoding lysosomal enzymes, protein co-factors or lysosomal membrane proteins. (bvsalud.org)
A metabolic disorder is any disease or disorder that negatively affects the biochemical reactions through which individual animal cells process nutrient molecules (such as the components of carbohydrates , proteins , and fats ) to yield energy or perform the functions necessary to sustain life (such as building complex molecules and creating cellular structure). (newworldencyclopedia.org)
Lysosomes4
All LSDs share the hallmark of waste product accumulation in the lysosomes, with the exact substrate varying depending on the disorder. (biologists.com)
Niemann-Pick disease type C (NPC) is a rare inherited lysosomal storage disease typified by accumulation of cholesterol and other lipids in late endosomes/lysosomes, thereby resulting in a spectrum of neurological, psychiatric, and systemic symptoms (notably liver disease). (biomedcentral.com)
At these sites, the Niemann Pick C1 cholesterol transporter (NPC1) facilitates the removal of cholesterol from lysosomes, which is then transferred to the ER for distribution to other cell membranes. (bvsalud.org)
Mutations in NPC1 result in cholesterol buildup within lysosomes, leading to Niemann-Pick Type C (NPC) disease, a progressive and fatal neurodegenerative disorder. (bvsalud.org)
Genes1
La enfermedad de Niemann-Pick tipo C (NPC) es un trastorno del metabolismo lisosomal que se debe a la presencia de variantes patogénicas bialélicas en los genes NPC1 o NPC2. (bvsalud.org)
Cholesterol7
Indeed, it has been demonstrated that HDAC inhibitors (HDACi) can impact cholesterol homeostasis in NPC1 disease models. (biologists.com)
However, exposure to 4 mM VPA resulted in a global reduction of cholesterol, indicating that VPA could be beneficial in correcting the NPC1 phenotype. (biologists.com)
Two hypotheses emerged from this observation: 1) a modest improvement in NPC1 trafficking can have a large impact on cholesterol homeostasis, or 2) that I1061T-NPC1 is destabilized upon reaching the LE/L compartment. (biologists.com)
We also study the NPC1 protein that is essential for cholesterol transport in humans and can lead to Niemann Pick C disease when mutated. (stanford.edu)
NPC1 N-terminus is the first luminal domain which binds to cholesterol and its oxygenated derivatives. (biomedcentral.com)
However, it is not fully understood how cholesterol is transported from NPC1 residing at the lysosomal membrane to the endoplasmic reticulum (ER) and plasma membrane. (bvsalud.org)
For example, in familial hypercholesterolemia, enzymes do not receive the signals that typically inhibit cholesterol synthesis, so that excessive production of cholesterol occurs, leading to early coronary vascular disease and strokes in patients. (newworldencyclopedia.org)
Neurodegenerative1
Niemann-Pick type C is an uncommon neurodegenerative lysosomal storage disorder that can cause a progressive neuropsychiatric syndrome associated with supranuclear vertical gaze palsy and a movement disorder. (bmj.com)
Disorder2
Niemann-Pick type C (NPC) is a disorder of the lysosomal metabolism due to biallelic pathogenic variants in NPC1 or NPC2. (bvsalud.org)
Type 2 Diabetes Mellitus, also known as insulin resistance, is related to diabetes mellitus and maturity-onset diabetes of the young, type 8, with exocrine dysfunction, and has symptoms including angina pectoris, tremor and equilibration disorder. (silexon.tech)
Abnormal1
In each case, the build-up of abnormal substrate is usually caused by a defect in a hydrolase, transporter, or activator. (biologists.com)
Therapeutic2
Treatment of NPC commonly consists of a multi-disciplinary therapeutic approach focused on symptom management and administration of substrate reduction therapy [ 10 ]. (biomedcentral.com)
Note: If you'd like to get a target analysis report for Diabetes Type 2 , or if you are interested to learn how our AI-powered BDE-Chem can design therapeutic molecules to interact with the target(s) above against the disease of Diabetes Type 2 at a cost 90% lower than traditional approaches, please feel free to contact us at [email protected] . (silexon.tech)
Neurological disease1
Multiple sclerosis is a common, chronic demyelinating neurological disease primarily affecting young adults, with a prevalence of ~0.1% in the Caucasian population (Miller and Leary, 2007). (medscape.com)
Metabolic disease1
Late onset of a metabolic disease is often triggered by acute metabolic stresses, such as infection, fasting, or consumption of a nutrient for which a metabolic intolerance exists. (newworldencyclopedia.org)
Secretion2
A molecular understanding of membrane traffic has broad implications for our understanding of growth control in cancer, receptor trafficking errors in heart disease, regulation of insulin secretion in diabetes and synaptic vesicle biogenesis and transport in neurological disorders. (stanford.edu)
NPC patients who participated in the interviews possessed a range of disease severity, central manifestations, and variable baseline characteristics such as age of symptom onset, age of diagnosis, current treatment, and geographical location. (biomedcentral.com)
This, in turn, is associated with a myriad of neurological / psychiatric and visceral symptoms, with wide variability in age of presentation, from prenatal / neonatal to adult-onset forms of the disease. (bvsalud.org)
Approximately 15% of patients follow a primary progressive or progressive relapsing course from disease onset, usually characterized by symptoms of progressive myelopathy (gait instability, spasticity, bladder symptoms) and cognitive impairment. (medscape.com)
Define2
Here we define the precise Rab29 binding region of the LRRK2 Armadillo domain between residues 360-450 and show that this domain, termed 'Site #1', can also bind additional LRRK2 substrates, Rab8A and Rab10. (stanford.edu)
information which can be used to optimize disease management and better define the scope of future clinical research studies. (biomedcentral.com)
Patient1
They treated control fibroblasts, along with NPC1 patient fibroblasts (one homozygous for the I1061T variant, and one heterozygous, P237S/I1061T) with DMSO or VPA for 48 hours. (biologists.com)
Insulin1
An important gene associated with Type 2 Diabetes Mellitus is IRS1 (Insulin Receptor Substrate 1), and among its related pathways/superpathways are Nervous system development and Angiopoietin-like protein 8 regulatory pathway. (silexon.tech)
Severe2
Some severe diseases, such as many of the lipid storage diseases, currently have no effective therapy. (newworldencyclopedia.org)
Legionella pneumophila is an accidental human bacterial pathogen that infects and replicates within alveolar macrophages causing a severe atypical pneumonia known as Legionnaires' disease. (microbialcell.com)
Domain3
The most common mutation, I1061T, is found in the largest lumen-facing domain, and causes mis-folding of the NPC1 protein. (biologists.com)
We also analyzed the evolutionary modularity of a data set of α -amylase catalytic domain homologs, and the dynamic modularity of the Niemann-Pick C1 (NPC1) protein N-terminal domain. (biomedcentral.com)
We were able to describe functional/structural sub-domain architecture related to key residues for starch cleavage, calcium, and chloride binding sites in the α -amylase, and sterol opening-defining modules and disease-related residues in the NPC1. (biomedcentral.com)
Years1
The last few years have seen considerable progress in understanding this disease and its management. (bvsalud.org)
Rare1
In this review, I will discuss how the study of these rare lysosomal disorders reveals unanticipated links to other rare and common human diseases using Niemann-Pick disease type C as an example. (bvsalud.org)
Function1
Here we show both in vitro and in an animal model of NPC disease that the loss of NPC1 function alters the distribution and activity of voltage-gated calcium channels (CaV). (bvsalud.org)
Found1
We have found that phosphorylation of Rab10 blocks primary cilia formation in culture and in certain brain regions and we would like to understand how this leads to Parkinson's disease. (stanford.edu)
Activity2
Our findings provide evidence that NPC is a nanostructural ion channel clustering disease, characterized by altered distribution and activity of ion channels at membrane contacts, which contribute to neurodegeneration. (bvsalud.org)
Diagnostic criteria and classification of multiple sclerosis subtypes have evolved in recent decades, and, although successive versions have differed in emphasis, all have required dissemination of disease in space (requiring involvement of multiple areas of the CNS) and in time (requiring ongoing disease activity over time). (medscape.com)
Includes1
This group includes lysosomal storage disorders, various mitochondrial diseases, other neurometabolic disorders, and several other miscellaneous disorders. (medscape.com)