title: Therapeutic Potential of Secreted Amyloid Precursor Protein APPsα.
abstract: Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory. While most early studies have been conductedin vitro, effectiveness in animal models is now being confirmed. These studies have revealed that either upregulating α-secretase activity, acutely administering APPsα or chronic delivery of APPsα via a gene therapy approach can effectively treat mouse models of Alzheimer's disease (AD) and other disorders such as traumatic head injury. Together these findings suggest the need for intensifying research efforts to harness the therapeutic potential of this multifunctional protein.
authors.affiliation: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago Otago, New Zealand.
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Mockett
authors.affiliation: Department of Functional Genomics, Institute for Pharmacy and Molecular Biotechnology, Heidelberg University Heidelberg, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Richter
authors.affiliation: Department of Psychology, Brain Health Research Centre, Brain Research New Zealand, University of Otago Otago, New Zealand.
authors.forename: Wickliffe C
authors.initials: WC
authors.lastname: Abraham
authors.affiliation: Department of Functional Genomics, Institute for Pharmacy and Molecular Biotechnology, Heidelberg University Heidelberg, Germany.
authors.forename: Ulrike C
authors.initials: UC
authors.lastname: Müller
keywords: APPsα; Alzheimer’s disease; amyloid precursor protein; neuroprotection; synaptic plasticity