Serum Markers of Type I Collagen Synthesis and Degradation in Amyotrophic Lateral Sclerosis

Abstract

Collagen abnormalities in the skin and spinal cord have been reported in amyotrophic lateral sclerosis (ALS) patients. Serum carboxyterminal propeptide of type I procollagen (PICP) and the carboxyterminal cross-linked telopeptide of type I collagen (ICTP) reflect type I collagen synthesis and degradation, respectively. However, there has been no study concerning PICP or ICTP in ALS. We studied collagen contents of the skin and measured serum levels of PICP and ICTP in patients with ALS and control subjects. Serum PICP levels were significantly lower in ALS patients than in controls. Serum ICTP levels were significantly higher in ALS patients than in controls, and there was an appreciable positive correlation between serum ICTP levels and the duration of illness in ALS patients. In ALS patients, the collagen content of the skin was significantly smaller than in controls and indicated a progressive decrease in relation to illness. In addition, there was a significant negative correlation between serum ICTP concentrations and the collagen content of the skin in ALS patients. These data suggest that increased ICTP levels and decreased serum PICP levels may reflect unique changes in the skin, with a predominance of degradation compared to the synthesis of type I collagen in ALS.

Linking neuron and skin: Matrix metalloproteinases in amyotrophic lateral sclerosis (ALS)

“…While type IV collagen is the main substrate for the gelatinases MMP-2 and -9 in the skin, a recent study indicated that MMP-9 is also able to digest type I collagen, which constitutes the major type of skin collagen [38]. Ono et al reported type I collagen metabolite changes in serum of ALS patients indicating a shift towards degradation of type I collagen [39]. The extent to which MMP-9 contributes to changes in type I collagen metabolism in ALS remains to be clarified by future studies.…”

Elevated prolidase activity in keloids: correlation with type I collagen turnover

“…It is well known that the amount of PINP generated during collagen synthesis is directly proportional to the amount of collagen produced 19,34 . PINP is released during collagen turnover, as is ICTP, a precursor molecule for cross‐linked collagen.…”

“…The aim of the present study was to understand the mechanism involved in the overproduction of type I collagen in keloids by studying key ECM components that are involved in the type I collagen catabolism pathway, such as the collagen catabolic products free proline, 18 aminoterminal propeptide of type I procollagen (PINP), a peptide generated during collagen synthesis, and carboxyterminal telopeptide of type I collagen (ICTP), a peptide generated following degradation of collagen fibrils 19,20 . In addition, the level of prolidase activity was measured.…”

Blood Biomarkers for Amyotrophic Lateral Sclerosis: Myth or Reality?

“…Thus, the concentration of the propeptide of type I procollagen, which is an index of collagen biosynthesis, appeared low in ALS patients. In contrast, the amount of the cross-linked telopeptide of type I collagen, which is an index of its degradation, was shown to be increased in a way that correlated with the disease duration [96]. Similarly, levels of type IV collagen also correlated with the duration of the disease [102].…”