Alpha-secretase helps in cleaving APP and hence eliminates the formation of beta-amyloid peptide and the left over APP that remains in the membrane is cleaved by gamma-secretase. What is the role of beta secretase in normal conditions?
It has to do with myelination.
http://www.ncbi.nlm.nih.gov/pubmed/16990514
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2493455/
Regards,
Joachim
Dear Jibin, First, beta-secretase generates Abeta peptides also in persons without AD. The exact physiological functions of Abeta are unclear, but may include synaptic pruning, especially important during the development of the nervous system, and probably with impact on synaptic plasticity throughout life. Second, the main beta-secretase enzyme, BACE1, has several substrates besides APP. Check out the EMBO J paper (2012) by Kuhn et al: http://www.ncbi.nlm.nih.gov/pubmed/22728825. The authors show that BACE1 may cleave a large number of membrane proteins, with have a central role for synapse formation.
BACE1 is involved in the processing of numerous substrates. In the brain, it is notably responsible for the cleavage and regulation of JAG1, one of the ligands of NOTCH1. BACE1-null mice exhibit a significant increase in astrogenesis (We et al, JBC, 2014). Moreover BACE1 cleavage of Neuregulin1 is critical for signaling functions in myelination, remyelination, synaptic plasticity, normal psychiatric behaviors, and maintenance of muscle spindles. (Hu X, et al. J Neurochem, 2016).
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