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Proteins for Conditioning Hair and Skin
Published in Randy Schueller, Perry Romanowski, Conditioning Agents for Hair and Skin, 2020
Elastin is the second most common connective tissue protein after collagen, constituting 60-80% of the dry weight of blood vessels and ligaments. Its unique amino acids are desmosine and isodesmosine. In skin, elastin fibers enmeshed in collagen provide skin with its elastic strength (23). Excessive sun exposure leads to abnormal, disoriented elastin fibers and folding of the epidermis (i.e., wrinkles) (26). Like hydrolyzed collagen, hydrolyzed elastin of 2000 to 5000 Da is a good film former, but is much less hygroscopic due to its much lower polar and charged amino acid content (see Tables 2 and 3). As a result it has much higher hydroalcoholic and polyol solubility and can reduce swelling of hair during permanent waving and coloring processes. Like other low-polarity protein hydrolyzates, such as silk (17), it may be preferable to collagen (and other more hydrophilic hydrolyzates) where humidity resistance is desirable.
Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Elastic fibres constitute important components of the extracellular connective tissues of the arterial wall. In the thoracic aorta, 40% of the total protein is elastic fiber, falling to about 20% in the abdominal portion. Elastin is produced in specialized mesenchymal cells, particularly in smooth muscle cells. Its immediate precursor is tropoelastin which is formed from a larger precursor, proelastin.549 Tropoelastin aggregates on microfibrils and lysine oxidase catalyzes the formation of covalent bonds between amino acids producing desmosine and isodesmosine.487
The Noncollagenous Proteins of the Intervertebral Disc *
Published in Peter Ghosh, The Biology of the Intervertebral Disc, 2019
Elastin is a highly insoluble protein rich in hydrophobic amino acids and contains few polar functional groups. It is synthesized as a soluble precursor molecule, tropoelastin (mol wt 72,000), of similar amino acid composition to insoluble elastin, but contains additional lysine residues which are subsequently involved in cross-link formation. These convert the tyopoelastin to insoluble elastin. Cross-linking is achieved via aldehyde (allysine) formation derived from lysine residues by the enzyme lysyloxidase. The cross-links of elastin contain the unique amino acids desmosine and isodesmosine.78,79 Other cross-links have recently been described,80–83 some of which are identical to those present in collagen.84 However, all of the known cross links of elastin are derived from lysine, whereas hydroxylysine is also utilized in collagen cross-link formation. In mature elastin, dihydrodesmosine and dihydroisodesmosine are more prevalent than the desmosine and isodesmosine ring structures. Problems, however, are encountered in the unequivocal demonstration of cross-linking structures in mature elastin, since the harsh extractive conditions required for its solubilization partially destroy desmosine/isodesmosine and intermediate cross-link structures.85,86
Gene therapy for alpha-1 antitrypsin deficiency: an update
Published in Expert Opinion on Biological Therapy, 2023
Debora Pires Ferreira, Alisha M Gruntman, Terence R Flotte
The progression of destruction of the lung tissue is currently being evaluated using both imaging and biochemical biomarkers. The measurement of computed tomography (CT) lung density has been particularly informative in studies of augmentation therapy, including the RAPID trial and the RAPID extension [76, 77]. In those studies, the rate of loss of lung density was reduced by nearly half among the group receiving an early start on augmentation therapy. The preservation of CT lung density corresponds with a preservation of pulmonary function by spirometry as well, but with less variability in the measurement. In a similar fashion, biochemical biomarkers of ECM loss have proven to be valuable outcome measures in evaluating the effects of therapies in this patient population. In particular, the measurement of desmosine and isodesmosine have correlated well with improvements in a wide range of pro-inflammatory cytokines, serum markers of protease/antiprotease imbalance and other indices of AAT biological activity [78].
Experimental and investigational drugs for the treatment of alpha-1 antitrypsin deficiency
Published in Expert Opinion on Investigational Drugs, 2019
As described in the introduction protease imbalance plays a key role in lung disease pathogenesis in AATD, driven by the lack of inhibition of NE by AAT. In addition, intravenous augmentation therapy, which appears clinically beneficial, reduces markers of NE activity (desmosine) [34], further confirming the importance of this pathway. Alvelestat (MPH-996), an oral NE inhibitor, is currently being trialed in Phase 2 clinical trials ASTRAEUS (NCT03636347) and ATALANTa (NCT03679598) which aim to reduce lung damage and slow the progression of lung disease caused by AATD. The primary endpoint is the change from baseline of desmosine/isodesmosine as biomarkers of NE activity. The rarity of AATD, and consequent need for surrogate outcomes if a study is to be of a reasonable size, has made markers like desmosine attractive as a primary outcome for phase 2 studies treating AATD lung disease.
Alpha 1 antitrypsin deficiency: a rare multisystem disease, predominantly affecting the lung
Published in Expert Opinion on Orphan Drugs, 2019
Priya S Chukowry, Ross Gareth Edgar, Alice M Turner
Another area to follow-up closely is the use of biomarkers in AATD COPD patients. Isodesmosine is an amino acid present in elastin and can be used as a marker of elastin degradation in AATD patients. The RAPID-RCT trial also showed that patients receiving augmentation therapy had statistically significant reductions in isodesmosine when compared to the placebo arm [74,103,104]. This correlation between a lung matrix injury biomarker and augmentation therapy suggests a therapeutic role for agents that can help preserve lung elastin structure and function. Hence, the therapeutic potential of aerosol hyaluronic acid, a glycosaminoglycan which possibly prevents elastin degradation by elastase, is currently being investigated as part of a clinical trial in AATD patients with emphysema (NCT03114020) [105].