Functions of amyloid precursor protein in metabolic diseases

• Published in: Metabolism, clinical and experimental Vol. 115; p. 154454
• Main Authors: Guo, Yanjun, Wang, Qinqiu, Chen, Shenghui, Xu, Chengfu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2021
• Subjects: Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein; Amyloid β; Animals; Humans; Metabolic disease; Metabolic Diseases - metabolism; APP; CTFβ; NAFLD; HFD; CNS; WAT; Metabolic disease; Aβ; GLUT-3; GLUT-1; AICD; ABAD; SCD1; GSI; LDLR; AD; T2D; HCC; IR; IGF-1; ER; SREBP-1c; ACC1; Amyloid precursor protein; BACE1; CVD; sAPPα; ChREBP; Amyloid β; ROS; sAPPβ; FAS
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2020.154454

Amyloid precursor protein (APP) is a transmembrane precursor protein that is widely expressed in the central nervous system and peripheral tissues in the liver and pancreas, adipose tissue, and myotubes. APP can be cleaved by proteases in two different ways to produce a variety of short peptides, each with different physiological properties and functions. APP peptides generated by non-amyloidogenic processing can positively influence metabolism, while the peptides produced by amyloidogenic processing have the opposite effects. Here, we summarize the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues. In addition, abnormal expression and function of APP and APP-derived peptides are associated with metabolic diseases, such as type 2 diabetes, obesity, non-alcoholic fatty liver disease, and cardiovascular disease, and cancers. Pharmacological intervention of APP function or reduction of the production of peptides derived from amyloidogenic processing may be effective strategies for the prevention and treatment of Alzheimer's disease, and they may also provide new guidance for the treatment of metabolic diseases. •APP is a transmembrane precursor protein that plays an important role in metabolism of the central nervous system and peripheral tissues.•Peptides produced by APP through non-amyloidogenic pathway have protective effects on metabolism, while peptides produced by the amyloidogenic pathway have detrimental effects.•Pharmacological intervention of APP or reduction of the peptides derived from amyloidogenic processing has benefical effects on AD and metabolic diseases.