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Zhou L, Barão S, Laga M, Bockstael K, Borgers M, Gijsen H, Annaert W, Moechars D, Mercken M, Gevaert K, Gevaer K, De Strooper B. The neural cell adhesion molecules L1 and CHL1 are cleaved by BACE1 protease in vivo. J Biol Chem. 2012 Jul 27;287(31):25927-40. PubMed.
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University College Dublin, Ireland
I really think these are interesting data, as they provide another possible neuroplastic mechanism to potentially explain the neurocognitive deficits associated with AD. In essence, it is proposed that BACE cleaves cell surface cell adhesion molecules, and in so doing, allows modification of the neural circuitry.
Most previous considerations [of synaptic changes in plasticity] have been related to endocytosis. Eric Kandel demonstrated this in vivo in the early 1990s, and later on we demonstrated the same in vivo. How endocytosis relates to Aβ-induced cognitive deficits is, of course, the next crucial step.
In this regard, we know that APP is internalized at two to six hours following a learning paradigm, and that this precedes the time when Aβ exerts its synaptotoxic effects on the newly formed learning-associated synapses. It may very well be that endocytosis or proteolytic release, as shown in the present paper, of cell adhesion molecules may facilitate a loosening of synaptic connections in the neural network and allow further remodeling of the circuitry—for good or for bad.
The next steps forward have to be most interesting.
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