REVIEW: IGF-Binding Proteins and Their Proteolysis as a Mechanism of Regulated IGF Release in the Nervous Tissue

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German A. Dya¹, Oleg I. Klychnikov¹, Daria A. Adasheva¹, Elizaveta A. Vladychenskaya¹, Alexey G. Katrukha¹, and Daria V. Serebryanaya^1,a*

¹Department of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received May 31, 2022; Revised July 24, 2022; Accepted August 2, 2022

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Insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) play a key role in the maintenance of the nervous tissue viability. IGF-1 and IGF-2 exhibit the neuroprotective effects by stimulating migration and proliferation of nervous cells, activating cellular metabolism, inducing regeneration of damaged cells, and regulating various stages of prenatal and postnatal development of the nervous system. The availability of IGFs for the cells is controlled via their interaction with the IGF-binding proteins (IGFBPs) that inhibit their activity. On the contrary, the cleavage of IGFBPs by specific proteases leads to the IGF release and activation of its cellular effects. The viability of neurons in the nervous tissue is controlled by a complex system of trophic factors secreted by auxiliary glial cells. The main source of IGF for the neurons are astrocytes. IGFs can accumulate as an extracellular free ligand near the neuronal membranes as a result of proteolytic degradation of IGFBPs by proteases secreted by astrocytes. This mechanism promotes interaction of IGFs with their genuine receptors and triggers intracellular signaling cascades. Therefore, the release of IGF by proteolytic cleavage of IGFBPs is an important mechanism of neuronal protection. This review summarizes the published data on the role of IGFs and IGFBPs as the key players in the neuroprotective regulation with a special focus on the specific proteolysis of IGFBPs as a mechanism for the regulation of IGF bioavailability and viability of neurons.

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KEY WORDS: neurons, astrocytes, IGF, IGFBP, proteolysis

DOI: 10.1134/S0006297923140079

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