Amyloid Beta Precursor Protein: Proper Credit for the Basic Biochemical Properties of the Most Studied Protein in the 21st Century*

Abstract

Listen

Translate article

Introduction The amyloid precursor protein (APP) is mainly known for being the precursor of the s-amyloid peptide, which accumulates in plaques found in the brain of Alzheimer’s disease patients. Expression in different tissues and the degree of sequence identity among mammals indicate an essential and non-tissue specific physiological function. APP is anchored to the membrane and displays a single C-terminal intracellular domain and a longer N-terminal extracellular domain. The basic biochemical properties and the scattered data on research, not related to production of beta-amyloid peptide, suggest that the protein and the molecules resulting from APP proteolytic cleavage may act as adhesion factors, enzymes, hormones/neurotransmitters and/or protease inhibitors. APP deserves to be known for its quite notable properties and its physiological role(s). Citation: Franco R, Navarro G, Martinez-Pinilla E, Moreno E (2014) Amyloid Beta Precursor Protein: Proper Credit for the Basic Biochemical Properties of the Most Studied Protein in the 21st Century. J Neurol Neurol Disord 1(1): 103 The number of papers related to amyloid precursor protein (APP) as of September 2014 is 30,075. Of those, papers in this Century are 24,390 (81% of the total), indicating that APP is one of the most studied proteins. Information is useful but excess of data may be counterproductive by the risk of losing the perspective to fully apprehend APP biological clues. A key issue in understanding APP biological relevance is to focus on its physiological role(s). As every other protein, APP may have different roles; a main one and other(s) possibly less relevant. This certainty drives scientific research. Due to enormous interest related to accumulation of a degradation peptide, beta-amyloid (As) peptide, in the brain of Alzheimer’s disease (AD) patients, APP research is biased towards the central nervous system (CNS) and mainly driven by its relationship with the amyloid-hypothesis of AD. The protein is widely expressed and is highly conserved among species; therefore its physiological function must be essential and non-tissue specific, i.e. not necessarily centered on the nervous system. In this perspective paper the focus is placed on aspects apparently attracting less interest in the field, namely the possibility of i) a relevant role of carbohydrates in APP function, ii) differential APP glycosylation in AD, iii) APP acting as adhesion molecule, iv) APP having enzyme activity, v) APP proteolytic cleavage providing polypeptides with hormone/neurotransmitter/growth factor potential, and vi) soluble APP acting as protease inhibitor in the CNS.