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 centra...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 13 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.展开更多
The natural design for the generation and the fate of proteins in an organism could be as complicated as life itself. A protein is biosynthesized strictly according to the message carried by the mRNA transcribed from ...The natural design for the generation and the fate of proteins in an organism could be as complicated as life itself. A protein is biosynthesized strictly according to the message carried by the mRNA transcribed from its gene. However, when, where, what and how much a gene is expressed are regulated precisely and dynamically at multiple levels, including at transcription, mRNA maturation, alternative splicing, and translation levels. A newly synthesized protein often needs to be further modified and sorted posttransla- tionally for its optimal confirmation and function. When a protein reaches its life span, the senescent protein is degraded by protein degradation machinery involving the ubiquitin-proteosome system and lysosomes. Protein homeostasis is essential for maintaining the normal mor- phology and function of the cell.展开更多
基金supported in part by the New York State Office for People with Developmental Disabilitiesthe Second Affiliated Hospital of the School of Medicine,Zhejiang Universitya grant from the U.S.Alzheimer’s Association(IIRG-10-170405)
文摘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 13 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.
文摘The natural design for the generation and the fate of proteins in an organism could be as complicated as life itself. A protein is biosynthesized strictly according to the message carried by the mRNA transcribed from its gene. However, when, where, what and how much a gene is expressed are regulated precisely and dynamically at multiple levels, including at transcription, mRNA maturation, alternative splicing, and translation levels. A newly synthesized protein often needs to be further modified and sorted posttransla- tionally for its optimal confirmation and function. When a protein reaches its life span, the senescent protein is degraded by protein degradation machinery involving the ubiquitin-proteosome system and lysosomes. Protein homeostasis is essential for maintaining the normal mor- phology and function of the cell.
