Therapeutic targets and delivery challenges for Alzheimer’s disease

Figure 3 Schematic representation of amyloid cascade hypothesis. Three enzymes α, β, and γ secretase play a crucial role in the proteolytic cleavage of APP. The first step, extracellular fragment of APP is cleaved by α-secretase (non-amyloidogenic and predominant pathway under normal condition) or β-secretase (amyloidogenic pathway predominant under AD) leading to 83 or 99 amino acid peptide residues respectively that remain attached as a trans membrane fragment. These fragments are ultimately cleaved by γ-secretase which leads to formation of toxic Aβ_(1-42) fragments in case of amyloidogenic pathway and initiates the extracellular Aβ plaque formation. APP: Amyloid precursor protein; AD: Alzheimer’s disease.