1Department of Neurology, Second Af? liated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
2Department of Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China
3Department of Neurochemistry, Inge Grundke-Iqbal Research Floor, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York 10314, USA

Abstract 

Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer’s disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

Keywords

Alzheimer‘s disease; APP metabolism; brain insulin signaling; glucose metabolism; memory and cognition; tau

[SpringerLink]