Transthyretin binding to A‐Beta peptide – Impact on A‐Beta fibrillogenesis and toxicity

Costa, Ana Rita; Gonçalves, Adriana; Saraiva, Maria João; Cardoso, Isabel

doi:10.1016/j.febslet.2008.02.034

Cited by 132 publications

(156 citation statements)

References 35 publications

Supporting

Mentioning

146

Contrasting

Order By: Relevance

“…In vitro studies have shown that TTR binds soluble Ab and prevents Ab amyloid fibril formation (53). In 2008, the Ab-TTR interaction was further characterized and it was shown that the inhibition/disruption of Ab fibrils by TTR could be one possible mechanism underlying the protective role of TTR in AD (54). Interestingly, as for apoA-I, further investigation on the TTR-Ab interaction revealed that TTR was able to cleave Ab.…”

Section: Ttr Binding To Lipoproteins and The Identification Of Apoa-imentioning

confidence: 99%

Aboard transthyretin: From transport to cleavage

et al. 2010

View full text Add to dashboard Cite

SummaryTransthyretin (TTR) is a plasma and cerebrospinal fluid protein mainly recognized as the transporter of thyroxine (T 4 ) and retinol. Mutated TTR leads to familial amyloid polyneuropathy, a neurodegenerative disorder characterized by TTR amyloid deposition particularly in peripheral nerves. Beside its transport activities, TTR is a cryptic protease and participates in the biology of the nervous system. Several studies have been directed at finding new ligands of TTR to further explore the biology of the protein. From the identified ligands, some were in fact TTR protease substrates. In this review, we will discuss the existent information concerning TTR ligands/substrates. 2010 IUBMB IUBMB Life, 62(6): [429][430][431][432][433][434][435] 2010

show abstract

Section: Ttr Binding To Lipoproteins and The Identification Of Apoa-imentioning

confidence: 99%

Aboard transthyretin: From transport to cleavage

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Recently, the proteolytic activity of TTR was discovered and its participation in the biology of the nervous system and high density lipoprotein (HDL) was demonstrated 8,9 . The cleavages of its particular substrates including amyloid β peptide (Aβ) and amidated neuropeptide Y (NPY) can lead to the protection of amyloidogenesis and the enhancement of nerve cell regeneration [10][11][12] . On the other hand, the TTR cleavage on apolipoprotein A-I (apoAI) promotes cholesterol efflux and increases amyloidogenicity of apoAI 13 .…”

Section: Introductionmentioning

confidence: 99%

Proteolytic activity of Crocodylus porosus transthyretin protease and role of the terminal polypeptide sequences

Leelawatwattana¹,

Praphanphoj²,

Prapunpoj³

2016

ScienceAsia

View full text Add to dashboard Cite

Human transthyretin (TTR), a recently identified protease, participates in the biology of high density lipoprotein and in the nervous system. In the present study, we determined whether TTR from a non-mammal Crocodylus porosus (crocTTR) has proteolytic activity and whether the N-and C-termini of the TTR polypeptide affect the proteolytic activity. The proteolytic activity of crocTTR and three chimeric crocTTRs: xenoN/crocTTR (crocTTR in which the N-terminal sequence was replaced with that of Xenopus laevis TTR), pigC/crocTTR (crocTTR in which the C-terminal sequence was replaced with that of Sus scrofa TTR), and xenoN/pigC/crocTTR (crocTTR in which the N-and C-terminal sequences were replaced with that of X. laevis TTR and S. scrofa TTR, respectively) were studied and compared. Using either casein or apoAI as a substrate, crocTTR had a lower proteolytic activity than human TTR. Replacing the C-terminal sequence of crocTTR increased the activity (casein: 1008 ± 36 pmol/min; apoAI: 231 ± 43 pmol/min), whereas replacing the N-terminal sequence decreased the activity (casein: 299 ± 26 pmol/min; apoAI: 31.5 ± 2.0 pmol/min). The activity of xenoN/pigC/crocTTR (casein: 502 ± 11 pmol/min; apoAI: 371 ± 23 pmol/min) was higher than those of crocTTR or xenoN/crocTTR, but similar to that of pigC/crocTTR. These results are the first to show the proteolytic activity of reptile TTR, and that the activity is changed when the N-and/or C-terminal amino acid sequences of the TTR subunit are changed.

show abstract

“…TTR has therefore been suggested to generally slow AD progression. TTR appears to be a major A␤-sequestering protein in human CSF, inhibiting and even reverting the formation of amyloid fibrils, as well as reducing their toxicity in vitro (58,59). TTR forms a complex with A␤ monomers/dimers, with stronger binding affinity observed for the more structurally flexible S85A TTR mutant (60), reinforcing the idea that less structured forms of amyloid proteins may be more likely to engage in cross-amyloid interactions.…”

Section: Transthyretinmentioning

confidence: 78%

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Luo

Wärmländer

Gräslund

et al. 2016

Journal of Biological Chemistry

125

108

View full text Add to dashboard Cite

Many protein folding diseases are intimately associated with accumulation of amyloid aggregates. The amyloid materials formed by different proteins/peptides share many structural similarities, despite sometimes large amino acid sequence differences. Some amyloid diseases constitute risk factors for others, and the progression of one amyloid disease may affect the progression of another. These connections are arguably related to amyloid aggregates of one protein being able to directly nucleate amyloid formation of another, different protein: the amyloid cross-interaction. Here, we discuss such cross-interactions between the Alzheimer disease amyloid-␤ (A␤) peptide and other amyloid proteins in the context of what is known from in vitro and in vivo experiments, and of what might be learned from clinical studies. The aim is to clarify potential molecular associations between different amyloid diseases. We argue that the amyloid cascade hypothesis in Alzheimer disease should be expanded to include cross-interactions between A␤ and other amyloid proteins.Alzheimer disease (AD) 3 is the most common form of elderly dementia. Its causes have not yet been clearly elucidated. The two classical AD lesions are depositions of intracellular neurofibrillary tau tangles and extracellular deposits of aggregated amyloid-␤ (A␤) peptides in amyloid plaques in the gray matter of the brain, mainly the hippocampus and neocortex. A␤ is a 36 -43-residue peptide cleaved from the amyloid-␤ protein precursor (A␤PP) by ␥-secretase and ␤-secretase enzymes.Some A␤PP and A␤ mutations increase A␤ production and deposition and/or extend the half-life of A␤ in the brain, but only a fraction (5%) of Alzheimer disease is familial AD (1). Several studies indicate that alterations of the pathologies of other amyloid proteins such as ␣-synuclein (2) and tau (3) are observed in familial AD.The amyloid cascade hypothesis suggests that deposition of A␤ aggregates in brain plays a vital role in AD development (4). The amyloid form of A␤ aggregates is generally defined by in vitro observations: originally by the so-called cross-␤ x-ray diffraction pattern or by observation of fibril structures in microscopy (transmission electron microscopy or atomic force microscopy) (5). Molecular probes recognizing the formation of certain ordered molecular structures include Congo red and thioflavin T, which change their optical properties when bound to amyloid material (5). The terms "on-pathway" and "off-pathway" intermediates are used to differentiate between self-aggregated A␤ species that lead to amyloid formation and those that do not. Missense mutations in the A␤PP, apoE, PS1, and PS2 genes can increase accumulation and toxicity of A␤ aggregates, and the "on-pathway" intermediate aggregates seem to be the most cell-damaging species (6). This provides strong support for the amyloid cascade hypothesis, which nevertheless remains disputed.Although two recent reviews (7, 8) respectively reject and support the amyloid cascade hypothesis, they both agree on one poin...

show abstract

Transthyretin binding to A‐Beta peptide – Impact on A‐Beta fibrillogenesis and toxicity

Cited by 132 publications

References 35 publications

Aboard transthyretin: From transport to cleavage

Aboard transthyretin: From transport to cleavage

Proteolytic activity of Crocodylus porosus transthyretin protease and role of the terminal polypeptide sequences

Cross-interactions between the Alzheimer Disease Amyloid-β Peptide and Other Amyloid Proteins: A Further Aspect of the Amyloid Cascade Hypothesis

Contact Info

Product

Resources

About