Role of insulin-like growth factor I signaling in neurodegenerative diseases.
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.
Trejo
José Luis
JL
Laboratory of Neuroendocrinology, Instituto Cajal, CSIC, Avda Dr Arce 37, 28002 Madrid, Spain.
Carro
Eva
E
Garcia-Galloway
Eva
E
Torres-Aleman
Ignacio
I
D001921:Brain / Q000473:pathology; D018450:Disease Progression; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000502:physiology*; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000473:pathology*; D009474:Neurons / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D007334:Insulin-Like Growth Factor I