A Novel <scp><i>NPTX1</i> de novo</scp> Variant in a Late‐Onset Ataxia Patient

Deppe, Jonas; Deininger, Natalie; Lingor, Paul; Haack, Tobias B.; Haslinger, Bernhard; Deschauer, Marcus

doi:10.1002/mds.28985

Cited by 2 publications

(2 citation statements)

References 7 publications

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“…The integration of the analyzed data sets enabled a focused selection of proteins of interest involved in synaptic dysfunction in the hippocampus of PD. Because NPTX1 and its receptor NPTXR were identified as differentially expressed and enriched in the synapto‐axonal WGCNA modules, and since NPTX1 has been associated with synaptic dysfunction in neurodegenerative diseases previously (Coutelier et al, 2021; Deppe et al, 2022; Figueiro‐Silva et al, 2015; Ma et al, 2018), and even proposed as an early biomarker for Alzheimer's disease (AD; Duits et al, 2018), we focused the further analysis on NPTX1 as a particularly promising target.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, deregulated expression of neuronal pentraxins (i.e., NPTX1 and NPTX2), as well as NPTXR, has been recently reported in a variety of neurological disorders, including AD, autosomal dominant cerebellar ataxia (ADCA) and frontotemporal dementia (FTD). (Coutelier et al, 2021;Deppe et al, 2022;Duits et al, 2018;Esteve et al, 2021;Figueiro-Silva et al, 2015;Ma et al, 2018). Recent studies also explored the biomarker potential of neuronal pentraxins and their receptors for neurodegenerative diseases (Duits et al, 2018;Dulewicz et al, 2021;Lim et al, 2019Lim et al, , 2020van der Ende et al, 2019van der Ende et al, , 2020.…”

Section: Discussionmentioning

confidence: 99%

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Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto‐axonal target in late‐stage Parkinson's disease

Warth Perez Arias,

Silbern,

Caldi Gomes

et al. 2023

Journal of Neurochemistry

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Parkinson's disease (PD) affects a significant proportion of the population over the age of 60 years, and its prevalence is increasing. While symptomatic treatment is available for motor symptoms of PD, non‐motor complications such as dementia result in diminished life quality for patients and are far more difficult to treat. In this study, we analyzed PD‐associated alterations in the hippocampus of PD patients, since this brain region is strongly affected by PD dementia. We focused on synapses, analyzing the proteome of post‐mortal hippocampal tissue from 16 PD cases and 14 control subjects by mass spectrometry. Whole tissue lysates and synaptosomal fractions were analyzed in parallel. Differential analysis combined with bioinformatic network analyses identified neuronal pentraxin 1 (NPTX1) to be significantly dysregulated in PD and interacting with proteins of the synaptic compartment. Modulation of NPTX1 protein levels in primary hippocampal neuron cultures validated its role in synapse morphology. Our analysis suggests that NPTX1 contributes to synaptic pathology in late‐stage PD and represents a putative target for novel therapeutic strategies.image

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto‐axonal target in late‐stage Parkinson's disease

Warth Perez Arias,

Silbern,

Caldi Gomes

et al. 2023

Journal of Neurochemistry

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A De Novo Missense NPTX1 Variant in an Individual with Infantile‐Onset Cerebellar Ataxia

et al. 2022

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2%). Other less common forms of ARCA represented 13% of the cases, including AOA type 1, ANO10, and STUB1 (Supplemental Material). This is the first multicentric study that provides information about epidemiology and frequency of ARCA in South America, and the largest ARCA frequency study worldwide. Our data are compatible with the literature regarding the most common forms of ARCA, but highlight the fact that ARSACS and NPC1 might be more common than previously thought, and provide the first real-world frequency estimates for the fairly recently identified RFC1 ARCA. 5 This study is limited by its retrospective nature. Also, it is possible that patients with undetermined ataxia are still poorly investigated through exome sequencing in South America. This, however, renders our population an interesting opportunity to identify new genes and knowledge on epidemiological features in ARCA. Moreover, our observations are relevant to the current planning of upcoming gene therapy and clinical trials in ARCAs.

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A Novel NPTX1 de novo Variant in a Late‐Onset Ataxia Patient

Cited by 2 publications

References 7 publications

Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto‐axonal target in late‐stage Parkinson's disease

Proteomic analysis of the human hippocampus identifies neuronal pentraxin 1 (NPTX1) as synapto‐axonal target in late‐stage Parkinson's disease

A De Novo Missense NPTX1 Variant in an Individual with Infantile‐Onset Cerebellar Ataxia

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