Familial Amyloid Polyneuropathy

Çakar, Arman; Durmuş-Tekçe, Hacer; Parman, Yeşim

doi:10.29399/npa.23502

Cited by 15 publications

(25 citation statements)

References 60 publications

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“…FAP, or transthyretin (TTR) amyloid polyneuropathy, is a progressive sensorimotor and autonomic neuropathy of adult onset, which is characterized by systemic accumulation of amyloid fibrils constituted of aberrant TTR protein [67]. The global prevalence is unknown, but in Japan it has been recently estimated to be around 1 person per million in the general population [68].…”

Section: Familial Amyloid Polyneuropathymentioning

confidence: 99%

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

et al. 2021

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The complement system is a key component of innate immunity since it plays a critical role in inflammation and defense against common pathogens. However, an inappropriate activation of the complement system is involved in numerous disorders, including peripheral neuropathies. Current strategies for neuropathy-related pain fail to achieve adequate pain relief, and although several therapies are used to alleviate symptoms, approved disease-modifying treatments are unavailable. This urgent medical need is driving the development of therapeutic agents for this condition, and special emphasis is given to complement-targeting approaches. Recent evidence has underscored the importance of complement component C5a and its receptor C5aR1 in inflammatory and neuropathic pain, indicating that C5a/C5aR1 axis activation triggers a cascade of events involved in pathophysiology of peripheral neuropathy and painful neuro-inflammatory states. However, the underlying pathophysiological mechanisms of this signaling in peripheral neuropathy are not fully known. Here, we provide an overview of complement pathways and major components associated with dysregulated complement activation in peripheral neuropathy, and of drugs under development targeting the C5 system. C5/C5aR1 axis modulators could represent a new strategy to treat complement-related peripheral neuropathies. Specifically, we describe novel C5aR allosteric modulators, which may potentially become new tools in the therapeutic armory against neuropathic pain.

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Section: Familial Amyloid Polyneuropathymentioning

confidence: 99%

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

et al. 2021

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“…Another risk factor for amyloidosis is mutation of a gene for which the non-mutated version encodes a protein that is non-fibrillogenic. Such mutations are at the root of several hereditary forms of amyloidosis [ 38 , 39 ]. The causative mutations either modify proteolytic cleavage of a precursor protein or alter the protein structure, resulting in proteins with intrinsic tendency to form amyloid fibrils.…”

Section: Causes Of Amyloidogenesismentioning

confidence: 99%

“…The causative mutations either modify proteolytic cleavage of a precursor protein or alter the protein structure, resulting in proteins with intrinsic tendency to form amyloid fibrils. In familial amyloid polyneuropathies (FAP), which are associated with peripheral neuropathy, mutations in the genes encoding TTR, gelsolin, or apolipoprotein A1 cause amyloid formation [ 39 , 40 ]. Amyloidosis (from the SAA protein) and peripheral neuropathy also occur in some familial autoinflammatory diseases, although the primary genetic defect in these syndromes does not occur in an amyloid protein gene [ 22 ].…”

Section: Causes Of Amyloidogenesismentioning

confidence: 99%

Amyloid Proteins and Peripheral Neuropathy

Asiri

Engelsman

Eijkelkamp

et al. 2020

Cells

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Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature—deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. Here, we will discuss how amyloid proteins contribute to peripheral neuropathy by reviewing the current understanding of pathogenic mechanisms in known inherited and acquired (usually rare) amyloid neuropathies. In addition, we will discuss the potential role of amyloid proteins in peripheral neuropathy in some common diseases, which are not (yet) considered as amyloid neuropathies. We conclude that there are many similarities in the molecular and cell biological defects caused by aggregation of the various amyloid proteins in these different diseases and propose a common pathogenic pathway for “peripheral amyloid neuropathies”.

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“…So far, more than 150 mutations have been described in the TTR gene. 5 The prevalence of different mutations varies according to ethnicity and geographic locations. TTR Val30Met mutation is the most common pathogenic variant overall.…”

Section: Introductionmentioning

confidence: 99%

Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study

Wang

et al. 2021

Ann Clin Transl Neurol

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Objective This study aims to report the genotypes and phenotypes of hereditary transthyretin amyloidosis (ATTR) in a large Chinese cohort, yet the clinical and genetic profiles of ATTR remain elusive in mainland China. Methods Fifty‐four patients with molecularly confirmed ATTR from 39 unrelated families were identified by sequencing the TTR gene. Sural nerve biopsies were performed in 40 of these cases. The clinical and electrophysiological data were retrospectively collected and analyzed. Results The male/female ratio was 42:12. The average age of patients at the onset of the disease was 47.8 ± 13.0 years. The late‐onset type occurred in 29 cases (53.7%). Twenty‐two probands (56.4%) had a family history with ATTR. The initial symptoms were limb paresthesia in 33 cases (61.1%), autonomic dysfunction in 15 cases (27.8%), and blurred vision in 6 cases (11.1%). A total of 22 different TTR mutations were identified, including Val30Met (25.6%) in 10 families in North China and Ala97Ser in 4 families (10.3%) in South China. Electrophysiological studies revealed general sensorimotor axonal polyneuropathy in 33/44 cases (75.0%), mixed neuropathy with axonal and demyelinating impairment features in 9/44 cases (20.5%) and isolated carpal tunnel syndrome in two cases. Sural nerve biopsies revealed positive Congo red staining in 16/40 cases (40.0%). Conclusion Chinese patients with ATTR exhibited heterogeneous TTR genotypes and clinical phenotypes. Val30Met remains the most common mutation type in mainland China.

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Familial Amyloid Polyneuropathy

Cited by 15 publications

References 60 publications

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives

Amyloid Proteins and Peripheral Neuropathy

Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study

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