RhyothemisOct 2, 2024

research article from 2011:

Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy
https://www.nature.com/articles/labinvest201171

"Human serum albumin, the most abundant protein in plasma, serves as a transporter of various ligands and an antioxidant in blood circulation. Human serum albumin is a mixture of a reduced form (human mercaptalbumin: HMA) and an oxidized form (human nonmercaptalbumin: HNA). Albumin is the major antioxidant in plasma, and a large proportion of all the serum antioxidant properties can be attributed to albumin. Previous work has shown the total reactive antioxidant potential in plasma, considered as an index of the level of antioxidants, decreased in patients with FAP. In addition, more recent work demonstrated that albumin suppressed amyloid formation of amyloid-β(Aβ), a component of amyloid fibrils in Alzheimer's disease, by reducing oxidative stress. These data suggest that albumin functing as an antioxidant may perform a crucial role in amyloid formation in FAP."

#amyloidosis #albumin #OxidativeStress

Loss of functional albumin triggers acceleration of transthyretin amyloid fibril formation in familial amyloidotic polyneuropathy - Laboratory Investigation

Transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP) is characterized by systemic accumulation of amyloid fibrils caused by a point mutation in the TTR gene. Despite the urgent need for alternative therapeutic strategies, the pathogenesis of FAP still remains elusive. In our study reported here, we focused on albumin, the most abundant protein in plasma, and described the role of albumin in the TTR amyloid-formation process. Patients with FAP evidenced significantly decreased serum albumin levels as the disease progressed. Biacore analysis showed that albumin had a binding affinity for TTR and exhibited higher affinity for TTR amyloid than native TTR. Albumin functioning as an antioxidant effectively suppressed TTR amyloid formation. In patients with FAP, albumin was significantly oxidized as the disease progressed. Moreover, loss of functional albumin accelerated TTR deposition in analbuminemic rats possessing a human variant TTR gene. Taken together, these results indicate that albumin may have an inhibitory role in the TTR amyloid-formation process.

Nature
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related, from 2012:

Serum albumin prevents protein aggregation and amyloid formation and retains chaperone-like activity in the presence of physiological ligands
https://pubmed.ncbi.nlm.nih.gov/22549788/

"Although serum albumin has an established function as a transport protein, evidence is emerging that serum albumin may also have a role as a molecular chaperone. Using established techniques to characterize chaperone interactions, this study demonstrates that bovine serum albumin: 1) preferentially binds stressed over unstressed client proteins; 2) forms stable, soluble, high molecular weight complexes with stressed client proteins; 3) reduces the aggregation of client proteins when it is present at physiological levels; and 4) inhibits amyloid formation by both WT and L55P transthyretin. Although the antiaggregatory effect of serum albumin is maintained in the presence of physiological levels of Ca(2+) and Cu(2+), the presence of free fatty acids significantly alters this activity: stabilizing serum albumin at normal levels but diminishing chaperone-like activity at high concentrations. Moreover, here it is shown that depletion of albumin from human plasma leads to a significant increase in aggregation under physiologically relevant heat and shear stresses. This study demonstrates that serum albumin possesses chaperone-like properties and that this activity is maintained under a number of physiologically relevant conditions."

#albumin #amyloid

Serum albumin prevents protein aggregation and amyloid formation and retains chaperone-like activity in the presence of physiological ligands - PubMed

Although serum albumin has an established function as a transport protein, evidence is emerging that serum albumin may also have a role as a molecular chaperone. Using established techniques to characterize chaperone interactions, this study demonstrates that bovine serum albumin: 1) preferentially …

PubMed
Oct 2, 2024 at 4:40pmWeb