Developmental Regulation of Amyloid Precursor Protein at the Neuromuscular Junction in Mouse Skeletal Muscle

APP Regulates Microglial Phenotype in a Mouse Model of Alzheimer's Disease

“…We recognize that A␤ peptide may be secreted from a variety of cells, including neurons (Busciglio et al, 1993;Takahashi et al, 2004), astrocytes (Siman et al, 1989;Haass et al, 1991), microglia (Banati et al, 1993b), or even peripheral cells for transport into the brain (Goldgaber et al, 1989;Farkas et al, 2003;Austin and Combs, 2010), where it may be responsible for the microglial activation associated with AD. Our data support the idea that APP may be able to generate its own ligand, oligomeric A␤, capable of regulating microglial phenotype in a paracrine or even autocrine fashion.…”

“…including the spleen, liver, skin, intestine, kidney, adipose tissue, heart, muscle, and thymus (Selkoe et al, 1988;Joachim et al, 1989;Yamada et al, 1989;Sandbrink et al, 1994;Akaaboune et al, 2000;Herzog et al, 2004;Galloway et al, 2007;Lee et al, 2008). We and others have also demonstrated that APP is expressed in immune cells, where it has a role in regulating cellular phenotype (Mönning et al, 1992;Bullido et al, 1996;Sondag and Combs, 2004;Vehmas et al, 2004;Carrano and Das, 2015).…”

Defective Neuromuscular Synapses in Mice Lacking Amyloid Precursor Protein (APP) and APP-Like Protein 2

“…Within the nervous system, APP can be detected on the membranes of synaptic preparations (Kirazov et al, 2001) and has been shown to localize to the postsynaptic densities, axons, and dendrites (Schubert et al, 1991;Shigematsu et al, 1992). APP undergoes rapid anterograde transport (Koo et al, 1990;Sisodia et al, 1993;Yamazaki et al, 1995) and is targeted to synaptic sites of both central and peripheral nervous systems, including neuromuscular junctions (NMJs) (Schubert et al, 1991;Shigematsu et al, 1992;Akaaboune et al, 2000).…”

Increased asynchronous release and aberrant calcium channel activation in amyloid precursor protein deficient neuromuscular synapses

“…It is highly expressed in central and peripheral nervous systems, and can be detected in both pre-and postsynaptic compartments (Akaaboune et al, 2000;Schubert et al, 1991;Shigematsu et al, 1992). Full-length APP is processed by at least three proteases termed α-, β-and γ-secretases; the combination of β-and γ-secretase processing leads to the liberation of β amyloid peptides (Reviewed by (Zheng, 2006)).…”