apoE and apoJ Presence and Potential Roles in CNS
Despite the fact that cholesterol is one of the most abundant molecules in the brain, accounting for approximately 10 of dry brain weight in contrast to less than 1 found in most other organs, surprisingly little is known about cholesterol and lipid transport and metabolism in the CNS. In addition to being a membrane component in the CNS, cholesterol is also found associated with lipoprotein particles in the CSF. Analysis of the constituents of human CSF provided the first information that...
David M Holtzman Mary Jo LaDu and Anne M Fagan
The intercellular transport of lipids through the aqueous circulatory system as well as within tissues and other body fluids requires the packaging of these hydrophobic molecules into water soluble carriers lipoproteins and their regulated targeting to appropriate tissues by receptor-mediated endocytic pathways as well as scavenger receptor-mediated pathways.1 Lipoproteins have been classified into several major groups on the basis of the density at which they float by ultracentrifugation. In...
Transgenic Analysis of Injury Response Elements in the Clusterin Locus
In the developing kidney, most tubular epithelial cells express clusterin. However, in the adult, only the distal convoluted tubules of the cortex express clusterin.3 As reviewed above, a defining feature of clusterin is its marked induction following renal and other organ injury. To begin an identification of clusterin gene regulatory elements involved in the response to kidney injury, we have subjected apoJCAT-1 mice to toxic amounts of folic acid. Acute renal tubular injury, induced by the...
Transgenic Analysis of Clusterin Gene Regulatory Elements
The most direct approach to identifying any gene's regulatory elements is to functionally demonstrate appropriate regulation upon inclusion of cloned segments of the gene into reporter gene constructions. Transgenic mouse technology offers a powerful initial approach. Whereas important clues can sometimes be obtained using DNA sequence analysis, DNase I hypersensitivity or reporter gene transfection into cell lines, these approaches are often very misleading. Transgenic mouse results are also...
Estrogen and Synaptic Sprouting The Role of Apolopoprotein E
Entorhinal cortex lesioning ECL is used as a model of the deafferenting aspects of AD. The outer 2 3 of the molecular layer of the dentate gyrus receive the majority of their input from the stellate neurons from layer 2 of the entorhinal cortex, which make up the majority of the perforant path.37 In ECL, the outer and middle molecular layers of the dentate gyrus are deafferented by transection or ablation of the perforant path. In the response to ECL, the molecular layer of the dentate gyrus is...
Potential Roles for apoE and apoJ in CNS Disease
Further studies to understand the structure and function of apoE and apoJ-containing lipoproteins produced by cells within the brain is likely to provide important insights into the role of these proteins in neurodegenerative and other diseases of the CNS. This issue will be considered in regard to Alzheimer's disease AD and brain repair following CNS injury. Genetic epidemiological studies have shown that the e4 allele of apoE is a major risk factor for AD.43 In addition, recent data suggests...
ClusterinapoJ An Apolipoprotein in Plasma and CSF
Lipoproteins have different protein called apolipoprotein and lipid compositions, and varying physiological activities as a result of this compositional heterogeneity. Apolipoproteins not only facilitate the binding of lipoprotein particles to specific cell surface receptors, but are also important in maintaining the structural integrity of lipoproteins and in modulating enzymatic reactions important in lipid cholesterol transport. One of the more recently identified apolipoproteins is...
In vitro Secretion of Clusterin by Cells of the CNS
The fact that clusterin immunoreactivity was observed in some neurons and glial cells does not prove that the protein is being synthesized by the positively-stained cells. The immunostaining could represent cell surface binding or uptake of clusterin. In order to identify the cell types that make and secrete clusterin in the brain, rat primary cultures from embryos or neonatal pups were used for investigation. By this means, both cortical and hippocampal astrocytes were shown to synthesize...