Introduction-
β –secretase (BACE1) is a transmembrane protein with its active site existing in the extracellular domain of the protein. It is made up of 2 aspartate residue Asp32 & Asp228. BACE-1 is a challenging target because it is an aspartyl protease with a site of action inside the central nervous system.. Alzheimer’s disease (AD) is the most common cause of dementia in elderly people, and the fourth most common cause of death in developed countries.AD is characterized by the formation of neurofibrillary tangles (NFT) from phosphorylated tau protein in the neurons and the deposition of β-amyloid (Aβ) plaque in the parenchyma of the amygdale, hippocampus and neocortex of the brain. The major …show more content…
Aβ is produced by a sequential cleavage of APP at the amino terminal end by β-secretase followed by γ-secretase at the carboxyl terminal end . β-secretase has been identified as an aspartic protease, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), also called Asp 2 (for novel aspartic protease 2) and memapsin 2 (for membrane aspartic protease/ pepsin 2). It is currently the most attractive target for the inhibition of amyloid production since it is the key enzyme that initiates the formation of Aβ. The development of β-secretase inhibitor drugs, however, has presented a different set of problems. On one hand, it is devoid of the function-based problems seen for γ-Secretase inhibitors. Elimination of β-secretase activity by gene deletion essentially abolished the production of Aβ, yet brought about only minor phenotypic abnormality in mice. This suggests that the activity of β-secretase can be