Proteins amyloid precursor protein

A universal postmortem hallmark of Alzheimer s disease (AD) is the presence of amyloid plaques in the brain. These plaques are mainly composed of a 39 to 42 amino acid peptide, referred to as A0 peptide, that is excised from a precursor protein, amyloid precursor protein (APP), by the sequential action of two proteases (Olsen et al., 2001). The first of the two cleavages of APP occurs at a site within the APP protein that is termed the P-site, and BACE has been clearly determined to be the enzyme responsible for this cleavage event. A small portion of the AD patient... 

Figure 11.1 The amyloid hypothesis in Alzheimer s disease. The transmembrane protein amyloid precursor protein (APP) is cleaved first by f> -secretase (BACE), then by y -secretase. The resulting peptidic fragment, AfSAO/42, is liberated, leading to plaque accumulation. These plaques are associated with neuronal degeneration.

Several measurements require the collection of nervous tissue at necropsy and homogenization of the tissues prior to analysis simple tissue procedures and associated measurements often do not indicate the localization of effects. Assays using tissue microdissection and in vitro cell cultures can help in the understanding of neurotoxic mechanisms, and these are being used more widely (Abdulla and Campbell 1992 Costa 1998 Harry et al. 1998). The development of assays such as neural gold protein, amyloid precursor protein, neuron specific enolase, heat shock proteins, and amyloid precursor proteins to study nervous diseases may find applications in some toxicology studies where the assays can be adapted for laboratory animals (de la Monte et al. 1997 Fitzpatrick et al. 2000 Rajdev and Sharp 2000). 

Munter LM, Voigt P, Harmeier A et al (2007). GxxxG motifs within the amyloid precursor protein transmembrane sequence are critical for the etiology of AB42. EMBO 126 1702-1712... 

Amyloid precursor protein (APP) is the precursor of (3-amyloid, the main component of senile plaques found in the brain of Alzheimer patients. The production of (3-amyloid from APP to the cells from abnormal proteolytic cleavage of the amyloid precursor protein. Enzymes involved in this cleavage may be suitable targets for the therapy of Alzheimer s disease. 

This type of disease occurs in families and begins unusually at early age (i.e., onset below the age of 60). Approximately 10% of Alzheimer s disease are familial and are inherited in an autosomal dominant manner with high penetrance. Deterministic genes directly cause the disease. Mutations in three different genes encoding for the amyloid precursor protein (APP) and the presenilins 1 and 2 (PS1 and PS2) have been identified to be responsible for early-onset familial Alzheimer s disease. 

Amyloid Precursor Protein Amyotrophic Lateral Sclerosis (ALS)... 

Abe, K., St. George-Hyslop, P.H., Tanzi, R.E., Kogure, K. (1991). Induction of amyloid precursor protein mRNA after heat shock in cultured human lymphoblastoid cells. Neurosci. Lett. 125, 169-171. 

Adlerz L., Soomets U., Holmlund L., Viiriaid S., Langel U., Iverfeldt K. Down-regulation of amyloid precursor protein by peptide nucleic acid oligomer in cultured rat primary neurons and astrocytes. Neurosci. Lett. 2003 336 55-59. 

Alzheimer s disease in which the pathogenicity of amyloid peptides depends on proteases, namely secretases, involved in amyloid precursor protein (APP) maturation. This chapter will describe how the proteolysis of chemokines might participate in the neuropathogenesis of HIV infection, thus contributing to the development of the central nervous system disorder termed HIV-associated dementia (HAD). 

Zhao M, Su J, Head E, Cotman CW (2003) Accumulation of caspase cleaved amyloid precursor protein represents an early neurodegenerative event in aging and in Alzheimer s disease. Neurobiol Dis 14 391-403... 

Most cases of AzD show cerebrovascular amyloid deposits and the amyloid protein of senile plaques is the same as that found in blood vessels. It is referred to as )S-amyloid protein and is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP, which is a transmembrane protein and although its precise function is not clear, it is widely distributed and APP knock-out mice show reduced motor function. Normally so-called short 40 amino-acid-soluble derivatives of APP are produced by proteolytic cleavage of APP within the j] (A4) amino-acid sequence but APP can also be cleaved... 

Figure 18.2 Production of senile plaque (S/A4 amyloid protein. Amyloid fS4 protein (/S/A4) is part of a 695, 751 or 770 amino-acid amyloid precursor protein APP. This is a transmembrane protein which is normally cleared within the fi/A4 amino acid sequence to give short 40 amino-acid soluble derivatives. It seems that under some circumstances as in Alzheimer s disease, APP is cleared either side of the fi/A4 sequence to release the 42/43 amino acid P/A4 which aggregates into the amyloid fibrils of a senile plaque (a). (See also Fig. 18.5.) Some factors, e.g. gene mutation, must stimulate this abnormal clearage leading to the deposition of P/A4 amyloid protein as plaques and tangles and the death of neurons (b)...

Checler, F (1995) Processing of the /i-amyloid precursor protein and its regulation in Alzheimer s disease. J. Neurochem. 65 1431-1444. 

Selkoe, D. J. (1998). The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer s disease. Trends Cell Biol. 8, 447-453. 

Davey FD, Breen KC. 1998. The interaction between chronic low-level lead and the amyloid precursor protein. Amyloid Int J. Clin Invest 5 90-98. 

Al = aluminium ApoE = apolipoprotein E APP = amyloid precursor protein. 

Figure 13.6. From left to right location of the P-amyloid region of amyloid precursor protein (APP) in relation to the neuronal membrane normal processing of APP inactivates P-amyloid abnormal processing of APP in Alzheimer s disease liberates intact P-amyloid.

Amyloid protein A 42-amino acid protein found in the core of the microscopic senile plaques in the brains of individuals with Alzheimer s disease, p-amyloid protein is synthesised from the much larger amyloid precursor protein (APP). 

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