Countering neurodegeneration by reducing the activity of the insulin/IGF signaling pathway: Current knowledge and future prospects

Human neurodegenerative maladies share two common key features: a mechanistic link to the accumulation and deposition of aberrantly aggregated proteins and late onset. These similarities among otherwise unrelated disorders suggest that the aging process plays an active role in enabling the emergence of these diseases late in life. Invertebrate-based studies have shown that the manipulation of aging by the reduction of the Insulin/IGF signaling (IIS), a prominent aging regulatory pathway, protects model organisms from neurodegeneration-linked toxic protein aggregation. Recent studies have also indicated that the counter proteotoxic effect of IIS reduction is conserved from worms to mice as reduced IGF-1 signaling protected Alzheimer's-model mice from the disease-like behavioral impairments, pathological phenotypes and premature death typical to these model animals. In this article I review the current knowledge on the protective mechanisms that are suppressed by the IIS and discuss the future therapeutic potential of IIS reduction as a treatment for neurodegenerative disorders. (C) 2010 Elsevier Inc. All rights reserved.