Journal of Molecular Medicine

, Volume 82, Issue 3, pp 156–162 | Cite as

Role of insulin-like growth factor I signaling in neurodegenerative diseases

  • José Luis Trejo
  • Eva Carro
  • Eva Garcia-Galloway
  • Ignacio Torres-Aleman
Review

Abstract

Disturbed trophic support to neurons has long been considered a potential mechanism in neurodegeneration. Recent evidence indicates that intracellular trophic signaling may be compromised in several neurodegenerative diseases. Changes in the levels of insulin-like growth factor I (IGF-I), a trophic hormone with multiple neuroprotective actions, have recently been observed in several human neurodegenerative illnesses. Therefore analysis of IGF-I pathways could help provide greater insight into trophic disturbances to neurons. However, neurodegenerative diseases with similar clinical manifestations show either high or low levels of circulating IGF-I. This apparently puzzling observation can be explained if we consider that IGF-I input to target neurons is disrupted by either lower IGF-I availability or by reduced cell sensitivity to IGF-I. The latter disturbance may be associated with high IGF-I levels. We hypothesize that in the majority of neurodegenerative diseases compromised IGF-I support to neurons emerges as part of the pathological cascade during the degenerative process and contributes to neuronal demise. In addition, loss of IGF-I input to specific neuronal populations might be the cause of a small group of neurodegenerative diseases.

Keywords

Insulin-like growth factor Intracellular trophic signaling Neurodegenerative diseases 

Abbreviations

AT

Ataxia-telangectasia

Amyloid-β

IGF

Insulin-like growth factor

IGFBP

Insulin-like growth factors binding protein

IRS

Insulin receptor substrate protein

LID

Liver IGF-1 deficiency

SCA

Spinocerebellar ataxia

TNF

Tumor necrosis factor

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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • José Luis Trejo
    • 1
  • Eva Carro
    • 1
  • Eva Garcia-Galloway
    • 1
  • Ignacio Torres-Aleman
    • 1
  1. 1.Laboratory of Neuroendocrinology, Instituto CajalCSICMadridSpain

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