Current and future treatment of amyloid neuropathies

Adams, David H.; Cauquil, Cécile; Théaudin, Marie; Rousseau, Antoine; Algalarrondo, Vincent; Slama, Michel

doi:10.1586/14737175.2014.983905

Cited by 23 publications

(21 citation statements)

References 77 publications

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“…39 Proteins can become prone to fibrillization because of aging or changes in the environmental conditions, such as crowding, pH or temperature shocks. In addition, point mutations can induce and often speed up fibrilization, such as in TTR V30M or L55P, [160][161][162][163][164][165] for the human prion protein (hPrP), 166 or for the homo-tetrameric p53 tumor suppressor protein. 167,168 Several lethal amyloidoses, e.g.…”

Section: Fibrillization And/or Amyloidosismentioning

confidence: 99%

A review on protein oligomerization process

Liu

2015

Int. J. Precis. Eng. Manuf.

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Enzymes or proteins are commonly present in oligomeric forms for active biological functions. The formation of protein oligomers, either in nature or by artificial means, can take place via covalent bonding or through weak-bond-network associations. Disulfide bonds are more common in forming covalent protein oligomers. Covalent bound protein oligomers usually have additional elements introduced, while proteins associated through weak-bond-networks usually do not involve any additional bound chemical groups. Proteins are commonly present in stable forms or folds. Oligomerization can occur when stable proteins unfold, creating exposed interfaces for association interactions. One well-known process of weak-bond-network oligomerization is domain swapping (DS). Separating the two touching/interacting domains creates opportunities for similar interactions with different protein molecules, leading to oligomerization. Both disulfide bonding and DS oligomerization can be dynamic (or reversible) at least at low Degree of Polymerizations (DPs). The dynamic nature of the protein oligomerization is important for bioactivity control. The morpheein model and the polymorph model are thus important in quantifying enzyme catalyzed biotransformations. Disulfide bonding and DS can act together to form supramolecules. The formation of supramolecules, such as amyloids, in nature can be benign or harmful. Industrial applications of protein oligomerization exploit the special functions /properties of the resultant supramolecules, such as multiple biofunctions, niche structure, etc..

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Section: Fibrillization And/or Amyloidosismentioning

confidence: 99%

A review on protein oligomerization process

Liu

2015

Int. J. Precis. Eng. Manuf.

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“…In fact, the pattern of clinical presentation depends on several factors, including genotype, the patient's geographical origin and age at symptom onset [11][12][13][14]. Genetic heterogeneity, clinical variability, and generally low prevalence frequently results in a delay in diagnosis of several years, especially in patients with a negative family history [15,16]. However, because of the severe natural course of ATTR-PN in endemic regions leading to disability and death within ten years, early diagnosis and treatment initiation are mandatory.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas

Thimm

Bolz

Fleischer

et al. 2019

Neurol. Res. Pract.

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Background: Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, genetically heterogenous, and clinically variable autosomal dominant disease that severely reduces life expectancy. As treatment options grow, a proper diagnostic approach is mandatory especially in non-endemic regions with diverse genetic backgrounds. Methods: We examined 102 neuropathy patients at a German neuromuscular centre. Common causes of polyneuropathy were ruled out by medical history and extensive laboratory testing to define a cohort of patients with progressive polyneuropathy classified as idiopathic. Molecular genetic testing of the entire TTR gene was performed, and the detected amyloidogenic and non-amyloidogenic variants were associated with the observed clinical phenotypes and results of prior diagnostic testing. Results: Two of 102 patients tested positive for amyloidogenic mutations (p.Ile127Val and p.Glu81Lys), while a variant of unknown significance, p.Glu26Ser, was found in 10 cases. In both positive cases, previous negative biopsy results were proved by gene sequencing to be false negative. In case of the p.Glu81Lys mutation we detected clinical presentation (combination of severe polyneuropathy and cardiomyopathy), ethnic background (patient of polish origin, mutation only reported in Japanese families before), and disease course clearly differed from wellknown cases of the same mutation in the literature. Conclusions: In conclusion, transthyretin hereditary amyloid polyneuropathy (ATTR-PN) should be considered in cases of otherwise idiopathic polyneuropathy. Sequencing of the four exons of the TTR gene should be considered the key step in diagnosis, while tissue biopsy possibly leads to false negative results.

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“…In most cases, no therapy is available at all. For one rare disease, familial amyloidotic polyneuropathy, the drugs tafamidis and diflunisal slow the disease progression [8]. For other diseases, such as AD, PD, and amyotrophic lateral sclerosis, drugs are available that offer moderate and temporary symptomatic relief, but not disease-modifying therapy.…”

Section: Introductionmentioning

confidence: 99%

Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins

Malik

Nair

et al. 2018

Methods in Molecular Biology

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Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein self-assembly, which act by binding selectively to lysine and arginine residues. Through this unique mechanism of action, MTs inhibit formation of toxic oligomers and aggregates. Their efficacy and safety have been demonstrated in vitro, in cell culture, and in animal models. Here, we discuss the application of MTs in diverse in vitro and in vivo systems, the experimental details, the scope of their use, and the limitations of the approach. We also consider methods for administration of MTs in animal models to measure efficacy, pharmacokinetic, and pharmacodynamic parameters in proteinopathies.

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Current and future treatment of amyloid neuropathies

Cited by 23 publications

References 77 publications

A review on protein oligomerization process

A review on protein oligomerization process

Prevalence of hereditary transthyretin amyloid polyneuropathy in idiopathic progressive neuropathy in conurban areas

Using Molecular Tweezers to Remodel Abnormal Protein Self-Assembly and Inhibit the Toxicity of Amyloidogenic Proteins

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