bace

Bace is a term that most often refers to beta-secretase enzymes in mammals, notably BACE1 and BACE2, members of the aspartyl protease family. These enzymes initiate the proteolytic processing of several transmembrane substrates, most prominently the amyloid precursor protein (APP).

BACE1 and BACE2 differ in tissue distribution and substrate preference. BACE1 is primarily expressed in neurons and catalyzes the cleavage of APP to produce the soluble APPβ fragment and the membrane-bound C99 fragment; C99 is then processed by gamma-secretase to release beta-amyloid peptides, which can aggregate in the brain. BACE2 has overlapping catalytic activity but a broader tissue expression and roles that are less clearly connected to Alzheimer's disease.

Clinical relevance: Because BACE1 activity contributes to beta-amyloid production, inhibitors were developed as potential disease-modifying treatments for Alzheimer's disease. Several BACE inhibitors reached late-stage trials, including verubecestat and lanabecestat, but came up short in demonstrating clinical benefit and were associated with adverse effects, leading to the halt of many programs. Ongoing research explores more selective inhibitors and strategies to minimize side effects, as well as non-APP substrates of BACE enzymes that influence neuronal function and myelination.

Other notes: The lowercase term bace is not widely used outside this biological context, and BACE is sometimes encountered as an acronym in other fields. In scientific literature, however, it most often denotes beta-secretase enzymes. See also Alzheimer's disease, beta-amyloid, and protease inhibitors.