New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis

Kiryu‐Seo, Sumiko; Nagata, Kenichi; Saido, Takaomi C.; Kiyama, Hiroshi

doi:10.1007/s11064-018-2665-x

Cited by 15 publications

(9 citation statements)

References 65 publications

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“…Altered abundance of transcripts involved in the response to calcium and calcium transport may imply abnormal calcium signaling. Conversely, some of these increased transcripts have also been implicated in promoting neuron regeneration and/or protecting against cell death, including Wnt5a (Subashini et al, 2017 ; Zhou et al, 2017 ), Dkk2 (Ghatak et al, 2017 ; Devotta et al, 2018 ), Crlf (Looyenga et al, 2013 ), Ecel (Kiryu-Seo et al, 2019 ), and Htlf (Helmer et al, 2013 ). The presence of increased transcripts associated with neuroprotection may reflect cells at different stages of response to prion replication with an early response to protect neurons followed by induction of cell death.…”

Section: Resultsmentioning

confidence: 99%

Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus

et al. 2022

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Progressive dysfunction and loss of neurons ultimately culminates in the symptoms and eventual fatality of prion disease, yet the pathways and mechanisms that lead to neuronal degeneration remain elusive. Here, we used RNAseq to profile transcriptional changes in microdissected CA1 and thalamus brain tissues from prion infected mice. Numerous transcripts were altered during clinical disease, whereas very few transcripts were reliably altered at pre-clinical time points. Prion altered transcripts were assigned to broadly defined brain cell types and we noted a strong transcriptional signature that was affiliated with reactive microglia and astrocytes. While very few neuronal transcripts were common between the CA1 and thalamus, we described transcriptional changes in both regions that were related to synaptic dysfunction. Using transcriptional profiling to compare how different neuronal populations respond during prion disease may help decipher mechanisms that lead to neuronal demise and should be investigated with greater detail.

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Section: Resultsmentioning

confidence: 99%

Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus

et al. 2022

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“…In some subjects, the ocular phenotypes are more prominent and the joint contractures do not meet the full diagnostic criteria for distal arthrogryposis ( Khan et al 2014 ; Shaaban et al 2014 ; Shaheen et al 2014 ). ECEL1 is a member of the neprilysin family of zinc metalloendopeptidases implicated in the final branching of axon nerve terminals and formation of neuromuscular junctions ( Kiryu-Seo et al 2019 ; Nagata et al 2016 ; Nagata et al 2017 ). The similarity of the phenotypes between subjects with ECEL1 mutations and the TUBB3 R262H syndrome may reflect the participation of ECEL1 and TUBB3 in a common pathway of axon guidance to distal muscles.…”

Section: Discussionmentioning

confidence: 99%

TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy

et al. 2021

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Microtubules are formed from heterodimers of alpha and beta tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3 , which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4(TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.

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“…There are at least 34 mutations in ECEL1 [2,6,7,18,19] (Figure 3). The structure of ECEL1 can be roughly divided into a cytoplasmic domain, a transmembrane domain, and an extracellular domain with a zinc binding motif (the 612 th -616 th AA) essential for enzymatic activity [6,7] [18,19]. G604R may have a similar pathogenicity.…”

Section: Discussionmentioning

confidence: 99%

The Novel Compound Heterozygous Mutations of ECEL1 Identified in a Family with Distal Arthrogryposis Type 5D

Jin

Liu

Jiao

et al. 2020

BioMed Research International

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Introduction. Distal arthrogryposis type 5D (DA5D) is an autosomal recessive disease. The clinical symptoms include contractures of the joints of limbs, especially camptodactyly of the hands and/or feet, unilateral ptosis, a round-shaped face, arched eyebrows, and micrognathia, without ophthalmoplegia. ECEL1 is a DA5D causative gene that encodes a membrane-bound metalloprotease. ECEL1 plays important roles in the final axonal arborization of motor nerves in limb skeletal muscles and neuromuscular junction formation during prenatal development. Methods. A DA5D family with webbing of the elbows and fingers was recruited. We performed whole-exome sequencing (WES) and filtered mutations by disease-causing genes of arthrogryposis multiplex congenita (AMC). Mutational analysis and cosegregation confirmation were then performed. Results. We identified novel compound heterozygous mutations of ECEL1 (NM_004826: c.69C>A, p.C23∗ and c.1810G>A, p.G604R) in the proband. Conclusions. We detected causative mutations in a DA5D family, expanding the spectrum of known ECEL1 mutations and contributing to the clinical diagnosis of DA5D.

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New Insights of a Neuronal Peptidase DINE/ECEL1: Nerve Development, Nerve Regeneration and Neurogenic Pathogenesis

Cited by 15 publications

References 65 publications

Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus

Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus

TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy

The Novel Compound Heterozygous Mutations of ECEL1 Identified in a Family with Distal Arthrogryposis Type 5D

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