The main lipids components of the cell membrane are the sphingolipids, cholesterol, and other phospholipids. The most predominant element of the sphingolipid molecule in the cell membrane is sphingomyelin, which is composed of a hydrophilic phosphorylcholine headgroup and a highly hydrophobic ceramide molecule. The ceramide group in sphingomyelin composed from amide ester of the sphingoid base D-erythro-sphingosine and a fatty acid of C16–C26 chain length. The lateral association of sphingolipids and cholesterol promoted by a strong interaction between the cholesterol sterol ring structure and the ceramide molecule of sphingomyelin, which are facilitated by hydrogen bonds and hydrophobic van der Waal interactions in addition to hydrophilic interactions and thus the split-up from other phospholipids into distinct microdomains (Brown & London, 1998). These microdomains have been termed rafts that play a function in aggregation of receptor molecules and the reorganization of intracellular signaling molecules to transmit a signal into the cell.
Sphingomyeline (SM) seems to be the main sphingolipid source for bioactive ceramide in the vast majority of cells, thereby stressing the major functions for ASMs in initiating ceramide signaling (Perrotta et al., 2010). ASM was initially recognized as a cation-independent hydrolase involved in the catabolism of SM in lysosomes (Horinouchi et al., 1995).Now there are two types of acid sphingomylinase. First is the lysosomal acid sphingomylinase(L-ASM) which has a major role in the production of ceramide as a response of the cell to stress such as infection, environmental insults, ligation of death receptors, and exposure to chemotherapy drugs. The transferring L-ASM to the lysosome is vi...
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...it is most obvious in endothelial cells. Probably, the absence of functional ASM inhibits the production of ceramide and reorganization of membrane rafts into platforms, protecting against cell death.
By introducing a partially functional SMPD1 gene onto the complete knockout (ASMKO) background, a transgenic mouse model of type B NPD has been produced, This results in a mouse with ~ 8 % residual ASM activity in most organs (Marathe et al., 2000 ). Notably, these mice never develop a neurological phenotype and live a normal lifespan. Nevertheless, by ~8–10 months of age they begin to show lipid storage in RES organs. These interpretations provide in vivo evidence that low levels of ASM activity in the brain are likely to prevent neurological disease in ASM patients, and have important applications for the treatment of neurological (type A )ASM-deficient NPD.
Margination and adhesion to the endothelium, in which accumulation of leukocytes occurs along the endothelial wall for adhesion. Afterward, these adhesions cause the separation of endothelial cells, allowing the leukocytes to extend and Transmigrate through the vessel walls. Followed by the response of chemical mediators(chemotaxis) that influence cell migration via an energy directed process which triggers the activation of Phagocytosis, in which monocytes, neutrophils, and tissue macrophages are activated to engulf and degrade cellular debris and
Lysosomes contain hydrolytic enzymes which function in the acid of the lysosome and are meant to be secreted not as wastes into the extracellular fluids, but as secretory proteins into an intracellular organelle. When one of these enzymes is dysfunctional, the catabolism of its macromolecule does not completely occur and there is a buildup of the macromolecule inside the lysosome. This results in great numbers of large lysosomes which begin to interfere with the normal functions of the cell. This disorder is called lysosomal storage disorder. These disorders can eventually lead to the dysfunction of the organs. The organs affected by the disorder are determined by two factors: 1) The location in the body where the macromolecules that are to be catabolized are found, and 2) The location where the catabolism occurs.
MS (Staley 2). Believed to retain “much of the characteristic form and expression of its
Neurodegeneration is used mainly for diseases that are characterised by progressive loss of structure and function of neurons. There are many neurodegenerative diseases including amyotrophic lateral sclerosis that...
It is not surprised that one of the common progressive motor neuronal disease, ALS, is also genetically connected to the mutations of degradation machineries with varied etiology. Even the majority of ALS is sporadic, two of familial ALS is mainly associated with simple monogenic factors, the mutation of SOD (D90A) and a large hexanucleotide (GGGGCC) repeat expansion in chromosome 9 open reading frame 72 (C9ORF72). However, growing evidence of genetic mutations in proteostasis factors discovered in familial ALS such as, UBQLN2, VCP/CDC48 in the UPS and SQSTM1/p62, VAPB and some of the vesicular traffic proteins in autophagy have been suggesting a fragile capacity of proteostasis in vulnerable neurons (Bedford et al., 2008; Deng et al., 2011; Paine et al., 2013; Johnson et al., 2010).
Around the world, many people are living with neurologically debilitating disorders like multiple sclerosis. Multiple sclerosis is best described as a pathological “inflammatory-mediated demyelinating disease of the human central nervous system,” and affects more than 2.5 million people globally (Trapp & Nave, 2008).
The above events end in cell death, including depletion of ATP, changes in ionic concentrations of sodium, potassium, and calcium, increased lactate, acidosis, accumulation of oxygen free radicals, intracellular accumulation of water, and activation of proteolytic processes.(Deb, Sharma, & Hassan, 2010). Surrounding this is the penumbra(Rodriguez-Yanez et al., 2006)
Its ability to inhibit sodium channels within brain cells thereby protecting the cells from hypoxia (lack of oxygen)
Lunn, J.S., Sakowski, S,A., Kim, B., Rosenberg, A.A., Feldman, E.L. (2009). Vascular endothelial growth factor prevents G93A-SOD1 induced motor neuron degeneration. Dev Neurobiology 69, 871-884
...on and forms an inhibitory complex with caveolin-1 leads to decrease in activity of enzyme in the cells. Transcription of Cav-1 gene is regulated by cholesterol responsive elements. Exposure of fibroblast and endothelial cells to free cholesterol and LDL Cholesterol was found to up regulate Cav-1 expression. Ca+2 mobilizing agents cause disinhibiton of e NOS by promoting Ca+2/Calmodulin triggered dissociation of Cav-1.
numerous diseases in mammals, all of which target the brain specifically. Also note that all prion-based
Multiple sclerosis is a chronic disease of the central nervous system. It is understood as an autoimmune disease, a condition where the body’s immune system mistakenly attacks normal tissues. In Multiple Sclerosis, the patient’s own cells & antibodies attack the fatty myelin sheath that protects and insulates nerve fibres in the brain and spinal cord, the two components of the CNS. This ultimately causes damage to the nerve cells and without the insulation the myelin sheath provides, nerve communication is disrupted. Hence, Multiple Sclerosis is characterized by symptoms that reflect central nervous system involvement (Luzzio, 2014).
Adrenoleukodystrophy is a genetically transferred disease which causes the human body to not be able to breakdown “very-long-chain-fatty-acids” (VLCFA). This inability to break down these acids eventually leads to myelin deterioration as well as the deterioration of the nervous system. Although there is no cure for this terrible disease, there are a variety of effective treatments.
plasma membranes, meaning animals and plants contain lipids. In this paper I will display and
Ongoing studies suggest there could be a correlation to malfunctioning genes that produce significant chemicals in the brain, which are responsible for the d...