Elastin-Derived Peptides in the Central Nervous System: Friend or Foe

Abstract

Elastin is one of the main structural matrix proteins of the arteries, lung, cartilage, elastic ligaments, brain vessels, and skin. These elastin fibers display incredible resilience and structural stability with long half-life. However, during some physiological and pathophysiological conditions, elastin is prone to proteolytic degradation and, due to the extremely low turnover rate, its degradation is practically an irreversible and irreparable phenomenon. As a result of elastin degradation, new peptides called elastin-derived peptides (EDPs) are formed. A growing body of evidence suggests that these peptides play an important role in the development of age-related vascular disease. They are also detected in the cerebrospinal fluid of healthy people, and their amount increases in patients after ischemic stroke. Recently, elastin-like polypeptides have been reported to induce overproduction of beta-amyloid in a model of Alzheimer's disease. Nevertheless, the role and mechanism of action of EDPs in the nervous system is largely unknown and limited to only a few studies. The article summarizes the current state of knowledge on the role of EDPs in the nervous system.

Keywords: Astrocyte; Elastin-derived peptides; Pparγ; Proliferation; ROS; VGVAPG.

Fig. 1

Scheme of VGVAPG peptide action in normal astrocytes

Fig. 2

Effect of the VGVAPG peptide on Ca²⁺ ion channels in astrocytes. The VGVAPG peptide acts through c-Src kinase and affects the N-methyl-d-aspartate receptor (NMDAR), L-type calcium channels (LTCC), and N-type calcium channels (NTCC), which increases the level of Ca²⁺ in the cell and finally increases the levels of reactive oxygen species (ROS). EBP elastin-binding protein; ERC elastin receptor complex; Neu1 neuraminidase; PPCA protective protein/cathepsin A

Fig. 3

Proposed mechanism of VGVAPG peptide action on MMP-2 and -9 and TIMP-1, -2, -3, and -4 expression in normal astrocytes. EBP elastin-binding protein; Neu1 neuraminidase; PPARγ peroxisome proliferator-activated receptor gamma; PPCA protective protein/cathepsin A

Fig. 4

Summary of the mechanism of VGVAPG peptide action in astrocytes with the crucial role of the PPARγ receptor. AhR: aryl hydrocarbon receptor; CAT: catalase; EBP: elastin-binding protein; eNos—endothelial nitric oxide synthase; IL-1β interleukin-1 beta; IL-1βR1 IL-1β—interleukin-1 beta receptor 1; iNos inducible nitric oxide synthase; Neu1 neuraminidase; NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells; nNos neuronal nitric oxide synthase; NO nitric oxide; PPARγ peroxisome proliferator-activated receptor gamma; PPCA protective protein/cathepsin A; ROS reactive oxygen species; SOD1 superoxide dismutase 1; VGVAPG Val-Gly-Val-Ala-Pro-Gly

Fig. 5

Scheme of VGVAPG peptide action on the production of progesterone (P₄), testosterone (T), and estradiol (E₂) in astrocytes. The scheme includes the role of c-Src kinase inhibitor I and the potential role of the aryl hydrocarbon receptor (AhR). EBP elastin-binding protein; Neu1 neuraminidase; PPCA protective protein/cathepsin A