The survival of rat cerebral cortical neurons in the presence of trophic APP peptides

Abstract

One function of Alzheimer amyloid protein precursor (APP) is the regulation of growth and differentiation in several types of cells, including fibroblasts, PC12 cells, and neurons. This activity is represented by a small stretch of amino acids in the center of the molecule around RERMS. The APP 17-mer peptide containing the RERMS domain supported survival and neurite extension of rat cortical neurons in a dose-dependent and sequence-specific manner. The APP fragment synthesized in Escherichia coli supported the survival and neurite extension of rat cortical neurons, whereas the mutant APP fragment lacking the 30 amino acids around the RERMS domain had drastically reduced activity to support the survival and neurite extension. The current study established APP as a neuron survival factor and determined that the sequence around RERMS is important for this function.

Amyloid Protein Precursor Stimulates Excitatory Amino Acid Transport

“…In vitro studies indicate that brain cells secrete roughly 10 -40% of their APP (12,13). Expressing full-length APPs in cultured cells or adding s-APP to their media promotes neurite outgrowth, enhances cell survival, and protects cells from a variety of cytotoxic agents (14,15).…”

ACAT1 regulates the dynamics of free cholesterols in plasma membrane which leads to the APP-α-processing alteration

“…In the α-processing, which is the major processing, APP is cleaved by α-secretase to produce a neurotrophic and neuroprotective fragment sAPPα [26,27], which has been demonstrated to have many beneficial functions, such as promoting neurite extension, enhancing neural cell survival, and protecting neurons from excitotoxin [28][29][30][31][32], whereas in the β-processing, which is the minor processing, APP is sequentially cleaved by β-and γ-secretases to produce amyloid β-peptides (Aβs) that deposit in brain as a neuropathologic hallmark of AD [33,34]. So far, the mechanistic understanding on the APP-α-processing is much less than that on the APP-β-processing.…”

Molecular and cellular mediators of Alzheimer's disease inflammation

“…The proinflammatory activity of sAβPP is inhibited by binding to ApoE, with ApoE3 being more effective than ApoE4. In contrast, it should be noted that sAβPP has also been demonstrated to have neurotrophic actions in many systems [24,262,266,291,292,373,463].…”