A key step in the processing of the integral membrane protein APP, or Amyloid Precursor Protein is through the proteolytic cleavage by the enzyme β-Secretase (BACE). The proteolysis of APP by BACE, followed by subsequent C-terminal cleavage(s) by γ-secretase, results in the formation of the amyloidβ(Aβ ) peptide. The principal component of the neuritic plaque found in the brains of Alzheimers Disease (AD) patients is Aβ which is a neurotoxic and highly aggregatory peptide segment of APP. The amyloid hypothesis holds that the neuronal dysfunction and clinical manifestation of AD is a consequence of the long term deposition and accumulation of 40-42 amino-acid long A β peptides, and that this process leads to the onset and progression of AD. Due to the apparent causal relationship between Aβ and AD, the so-called "secretases" that produce Aβ have been targeted for development of inhibitors that might serve as therapeutic agents for treatment of this dreaded, and ever more prevalent disease. Herein will be discussed our current understanding of BACE, its role in the formation of neuritic plaques and the known inhibitors of the enzyme.
Keywords: amyloidogenic pathway, Alzheimer, ’, s disease, Hydroxyethylene inhibitors, APP processing, hydroxymethylcarbonyl (HMC)
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