|
|
|
|
Presenilins (PS-1 & PS-2) Antibodies
Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognition in the elderly. A number of genes have been linked in the initiation and development of AD. One of the most important and initial step involves proteolytic cleavage of amyloid precursor protein (APP, chromosome 21) releasing short 40, 42 & 43 aa peptides (b amyloid 1-40, 1-42, and 1-43). Polymerization of b-amyloid (Ab) and subsequent neuronal deposit (amyloid) leads to the degeneration of neurons involved in memory and cognition. Mutations in the APP gene cause some forms of familial AD (FAD) by releasing an increased amounts of b-amyloid. The AD Ab deposits also contain anti-chymotrypsin (ACT), and Apolipoprotein (Apo-E) that may promote Ab polymerization. Although, Ab deposits or plaques are central to neuropathogenesis and neurodegeneration, it is not clear how it affect neuronal functions. Most recently, an intracellular protein termed ERAB (Endoplasmic reticulum associated binding protein on chromosome X) has been cloned and linked with Ab neurotoxicity. An early onset of FAD has also been linked to some 30 mutations in two related genes, Presenilins-1 (PS-1 on chromosome 14; 467 aa) and Presenilins-2 (PS-2 on chromosome 1; 448 aa). Presenilins may contain 7-9 transmembrane domains. Presenilins are members of an evolutionary conserved gene family. PS1 and PS2 are 67% identical, and show significant homology to C. elegans genes sel-12 (~50 homology) and spe-4 (~20% identity). Both PS1 and PS2 genes are expressed in several human and rat tissues. In the CNS, the two genes are predominately expressed in neurons. Have PS-1/2 have been co-localized in subcellular sites involved in cell cycle regulation and mitosis (the nuclear membrane, interphase kinetochore, and centrosome). Apo E, a component
of lipoproteins produced by the liver and in circulating macrophages, plays a
critical role in the reverse transport of cholesterol to the liver via the
circulation. ApoE is a single polypeptide chain of 299 amino acids (~34 kDa)
consisting of two independently folded functional domains. Humans and mice
lacking apoE cannot clear remnant lipoproteins from the plasma and are at
increased risk for atherosclerosis. In humans, apoE has three major isoforms:
Apo E2 (Cys112, Cys158), Apo E3 (Cys112, Arg158), Apo E4 (Arg112, Arg158),
products of alleles at a single gene locus. Although apoE4 is neither necessary
nor sufficient to cause AD, inheritance of apoE4 is a significant risk factor
for late onset AD.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|