Neuroprotective effects of a locally acting IGF-1 isoform

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Exp Gerontol. 2006 Jun 16

The neuroprotective effects of a locally acting IGF-1 isoform.

Musaro A, Dobrowolny G, Rosenthal N.

Department of Histology and Medical Embryology, CE-BEMM and

Interuniversity Institute of Myology, University of Rome " La

Sapienza " , Italy; Edith Cowan University, Western Australia,

Australia.

In the last decade, dramatic progress has been made in elucidating

the molecular defects underlying a number of neuromuscular diseases.

With the characterization of mutations responsible for muscle and

nerve dysfunction in several inherited pathologies, and the

identification of novel signaling pathways, in which subtle

alterations can lead to significant defects in tissue metabolism, the

field is poised to devise successful strategies for treatment of this

debilitating and often fatal group of human ailments.

Yet progress in therapeutic application has been slow despite our

newly gained knowledge of basic biology. Hence, where direct

therapeutic approaches to address the primary diseases are still sub-

optimal, it may be more effective to focus on strategies for

improving neuromuscular function.

Among potential candidates, insulin-like growth factor (IGF-1) has

been involved in several anabolic pathways in both skeletal muscle

and the nervous system and it is a promising candidate to attenuate

neuromuscular diseases. In this review, we will discuss the role of

IGF-1 isoforms in neuromuscular diseases and the contribution of

muscle-produced IGF-1 (mIGF-1) to motor neuron survival and activity.