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

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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.

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Abbreviations

AT :

Ataxia-telangectasia

Aβ :

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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Authors and Affiliations

  1. Laboratory of Neuroendocrinology, Instituto Cajal, CSIC, Avda. Dr. Arce 37, 28002, Madrid, Spain

    José Luis Trejo, Eva Carro, Eva Garcia-Galloway & Ignacio Torres-Aleman

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  1. José Luis Trejo
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  2. Eva Carro
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  3. Eva Garcia-Galloway
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  4. Ignacio Torres-Aleman
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Correspondence to Ignacio Torres-Aleman.

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Trejo, J.L., Carro, E., Garcia-Galloway, E. et al. Role of insulin-like growth factor I signaling in neurodegenerative diseases. J Mol Med 82, 156–162 (2004). https://doi.org/10.1007/s00109-003-0499-7

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  • DOI: https://doi.org/10.1007/s00109-003-0499-7

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