6.3 Amyloid Theory

6.3 Amyloid Theory

6.3 Amyloid theory The most commonly supported hypothesis for the cause of AD relates to a protein expressed in many cells, of unknown function and implicated in familial AD due to mutations in the gene that code for it(Wisniewski, Wisniewski & Wen 1985). Although its function is not completely understood, –amyloid precursor protein (APP) is suggested to be critical for neuron growth(Turner et al. 2003, Vasto et al. 2008, Priller et al. 2006), signalling, and may also function as an antioxidant(Crouch 2007) and a metalloprotein, modulating copper transport and metabolism(Turner et al. 2003, Priller et al. 2006, Kong et al. 2007). The parent protein, the 695–770 amino acid APP, in most cell types undergoes the non–amyloidogenic pathway. Cleavage of the APP protein can occur at many sites within the cell, including the trans–Golgi network, ... Show more content on Helpwriting.net ...The amyloidogenic version of the pathway involves cleavage by –secretase followed by the –secretase (see figure 6), releasing the 40–43 amino acid amyloid beta (A) peptide, thought to cause the neurodegenerative disease(Selkoe 2001, Findeis 2007). The enzymatic action of –secretase leaves a C–terminal fragment known as APP–CTF or

C99, within the membrane and releases APPs into the extracellular space. After A peptide generation by –secretase from the C99 fragment, the A peptide is extracellularly secreted(Rogaeva et al. 2007). Most of the A peptides produced are 40 amino acids long, however it is thought in the diseased state the usual 10% of A peptide production increases, causing havoc within the cell and the surrounding environment(Vasto et al. 2008). This longer form

(A

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) is more hydrophobic and fibrillates more easily, and is also controversially thought to be more neurotoxic than the A peptide(Selkoe 2001, Findeis

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