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Table 1 Validated BACE1 substrates and potential mechanism-based toxicity arising from BACE1 inhibition

From: The β-secretase enzyme BACE1 as a therapeutic target for Alzheimer's disease

Substrate Toxicity
APP, APLP1 and APLP2 Impaired cell-cell signaling, injury recovery, synaptic function, memory
IL1R2 Abnormal inflammatory response
LRP Impairments in lipid metabolism, degradation of proteases and activation of lysosomal enzymes
Navβ1-4 Altered neuronal excitability [76]
Neuregulin-1 and neuregulin-3 Impaired remyelination following nerve injury [58]
PSGL-1 Altered leukocyte recruitment during innate and adaptive immune response [77]
ST6Gal I Hepatopathology, B-cell dysfunction
  1. APLP, amyloid beta precursor-like protein; APP, amyloid precursor protein; BACE1, β-site amyloid precursor protein cleaving enzyme 1; IL1R2, IL-1 type II receptor; LRP, low-density lipoprotein receptor-related protein; Navβ1-4, voltage-gated sodium channel β1 to β4 subunits; PSGL-1, P-selectin glycoprotein ligand-1; ST6Gal I, Golgi-localized membrane-bound β-galactoside α2,6-sialyltransferase.