Indeed, hTTR amyloid fibrils were found in 25% of post-mortem hearts from patients >80 years of age 11. Recent data suggest that SSA-related cardiomyopathy has been often overlooked as a common cause of heart failure in older adults 12, 13, 14, 15, 16, 17, 18. Nevertheless, the prevalence of ATTR in Europe is 75 years), it is generally associated to cardiomyopathic complications, and leads to progressive heart failure 10, 11. ATTR is a rare hereditary disorder with a relatively early age of onset, usually 100 single point mutations affecting the hTTR gene and it has been recognized as the most common cause of hereditary amyloidosis worldwide 9. HTTR is one of the 25 proteins related to the onset of amyloid-based diseases 5 and, indeed, hTTR aggregation causes amyloidosis, which is associated to two different pathological conditions, i.e., familial amyloidosis (ATTR) and senile systemic amyloidosis (SSA) 6. The two dimers then weakly interact to form the final tetrameric structure, stabilized by hydrophobic interactions involving the A-B and G-H loops 2, 3, 4. The monomers tightly interact, mainly through hydrogen bonds networks between adjacent antiparallel β-strands H-H′ and F-F′, to form stable dimers. Each β-sheet is formed by four strands (β-sheet I: H-G-A-D strands β-sheet II: C-B-E-F strands), while the α-helix is located between strands E and F 2, 3, 4. Each hTTR monomer consists of 127 amino acids and forms eight β-strands, named from A to H, which are arranged in a β-sandwich of two β-sheets (I and II) and one small α-helix. In its native tetrameric conformation, hTTR transports thyroid hormones in the blood and cerebrospinal fluid along with retinol as a binding partner of retinol binding protein 1. Human transthyretin (hTTR) is a 55-kDa homotetrameric protein, mainly produced in the liver and brain, and abundantly present in human plasma (0.18–0.45 mg/ml) 1. To the best of our knowledge, these findings highlight a novel pathogenic mechanism for SSA whereby increased permeability of the gut mucosa, as often occurs in elderly people, allows subtilisin (and perhaps other yet unidentified bacterial proteases) to reach the bloodstream and trigger generation of hTTR fragments, acting as seeding nuclei for preferential amyloid fibrils deposition in the heart. Here, we show that subtilisin secreted from Bacillus subtilis, a gut microbiota commensal bacterium, translocates across a simulated intestinal epithelium and cleaves hTTR both in solution and human plasma, generating the amyloidogenic fragment hTTR(59–127), which is also found in SSA amyloids in vivo. Fragmented hTTR is the standard composition of amyloid deposits in SSA, but the protease(s) responsible for amyloidogenic fragments generation in vivo is(are) still elusive. Send us feedback about these examples.Aggregation of human wild-type transthyretin (hTTR), a homo-tetrameric plasma protein, leads to acquired senile systemic amyloidosis (SSA), recently recognised as a major cause of cardiomyopathies in 1–3% older adults. These examples are programmatically compiled from various online sources to illustrate current usage of the word 'proteolysis.' Any opinions expressed in the examples do not represent those of Merriam-Webster or its editors. 2011 This action of protein breakdown ( proteolysis) determines the structure and sensory properties of Parmigiano Reggiano and its high digestibility. Rebecca Kreston, Discover Magazine, 4 Nov. 2017 Using proton pumps and acid phosphatases, the parasite is able to resist degradation by proteolysis, further ensuring its survival within the macrophage. Ashton Yoon, Discover Magazine, 26 Sep. Catherine Hu, Discover Magazine, The three primary reactions that define cheese ripening are glycolysis, proteolysis, and lipolysis. Recent Examples on the Web Real meats contain glutamate as it is found in proteins, and it is released during proteolysis that occurs during meat aging and cooking.
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