Aging of the brain, neurotrophin signaling, and Alzheimer's disease: Is IGF1-R the common culprit?

NEUROBIOLOGY OF AGING

卷:29

Review

Puglielli, Luigi^1,2 

[1] Univ Wisconsin, Dept Med, Madison, WI 53705 USA

[2] VA Med Ctr, Geriatr Res Educ Clin Ctr, Madison, WI 53705 USA

关键词: aging;    Alzheimer's disease;    IGF1-R;    neurotrophin receptors;    amyloid beta-peptide;   

DOI  :  10.1016/j.neurobiolaging.2007.01.010

来源: Elsevier

【 摘 要 】

The last decade has revealed that the lifespan of an organism can be modulated by the signaling pathway that acts downstream of the insulin/insulin-like growth factor I receptors (IR/IGF1-R), indicating that there is a program that drives the process of aging. New results have now linked the same pathway to the neurogenic capacities of the aging brain, to neurotrophin signaling, and to the molecular pathogenesis of Alzheimer's disease. Therefore, a common signaling cascade now seems to link aging to age-associated pathologies of the brain, suggesting that pharmacologic approaches aimed at the modulation of this pathway can serve to delay the onset of age-associated disorders and improve the quality of life. Work from a wide range of fields performed with different approaches has already identified some of the signaling molecules that act downstream of IGF1-R, and has revealed that a delicate checkpoint exists to balance excessive growth/immortality and reduced growth/senescence of a cell. Future research will determine how far the connection goes and how much of it we can influence. (C) 2007 Elsevier Inc. All rights reserved.

【 授权许可】

Free