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Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery

Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such a...

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Autores principales: Zhao, Yuhai, Arceneaux, Lisa, Culicchia, Frank, Lukiw, Walter J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651065/
https://www.ncbi.nlm.nih.gov/pubmed/34881359
http://dx.doi.org/10.24966/AND-9608/100056
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author Zhao, Yuhai
Arceneaux, Lisa
Culicchia, Frank
Lukiw, Walter J
author_facet Zhao, Yuhai
Arceneaux, Lisa
Culicchia, Frank
Lukiw, Walter J
author_sort Zhao, Yuhai
collection PubMed
description Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components. Down-regulated NF-L in neurons correlates well with the observed axonal and neuronal atrophy, neurite deterioration and synaptic disorganization in tissues affected by Alzheimer’s disease (AD) and other progressive, age-related neurological diseases. This Review paper: (i) will briefly assess the remarkably high number of neurological disorders that exhibit NF-L depolymerization, liberation from neuron-specific compartments, mobilization and enrichment into pathological biofluids; (ii) will evaluate how NF-L exhibits compartmentalization effects in age-related neurological disorders; (iii) will review how the shift of NF-L compartmentalization from within the neuronal cytoskeleton into peripheral biofluids may be a diagnostic biomarker for neuronal-decline in all cause dementia most useful in distinguishing between closely related neurological disorders; and (iv) will review emerging evidence that deficits in plasma membrane barrier integrity, pathological transport and/or vesicle-mediated trafficking dysfunction of NF-L may contribute to neuronal decline, with specific reference to AD wherever possible.
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spelling pubmed-86510652021-12-07 Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery Zhao, Yuhai Arceneaux, Lisa Culicchia, Frank Lukiw, Walter J HSOA J Alzheimers Neurodegener Dis Article Neurofilaments (NFs) are critical scaffolding components of the axoskeleton of healthy neurons interacting directly with multiple synaptic-phosphoproteins to support and coordinate neuronal cell shape, cytoarchitecture, synaptogenesis and neurotransmission. While neuronal presynaptic proteins such as synapsin-2 (SYN II) degrade rapidly via the ubiquitin-proteasome pathway, a considerably more stable neurofilament light (NF-L) chain protein turns over much more slowly, and in several neurological diseases is accompanied by a pathological shift from an intracellular neuronal cytoplasmic location into various biofluid compartments. NF-L has been found to be significantly elevated in peripheral biofluids in multiple neurodegenerative disorders, however it is not as widely appreciated that NF-L expression within neurons undergoing inflammatory neurodegeneration exhibit a significant down-regulation in these neuron-specific intermediate-filament components. Down-regulated NF-L in neurons correlates well with the observed axonal and neuronal atrophy, neurite deterioration and synaptic disorganization in tissues affected by Alzheimer’s disease (AD) and other progressive, age-related neurological diseases. This Review paper: (i) will briefly assess the remarkably high number of neurological disorders that exhibit NF-L depolymerization, liberation from neuron-specific compartments, mobilization and enrichment into pathological biofluids; (ii) will evaluate how NF-L exhibits compartmentalization effects in age-related neurological disorders; (iii) will review how the shift of NF-L compartmentalization from within the neuronal cytoskeleton into peripheral biofluids may be a diagnostic biomarker for neuronal-decline in all cause dementia most useful in distinguishing between closely related neurological disorders; and (iv) will review emerging evidence that deficits in plasma membrane barrier integrity, pathological transport and/or vesicle-mediated trafficking dysfunction of NF-L may contribute to neuronal decline, with specific reference to AD wherever possible. 2021-10-13 2021 /pmc/articles/PMC8651065/ /pubmed/34881359 http://dx.doi.org/10.24966/AND-9608/100056 Text en https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Article
Zhao, Yuhai
Arceneaux, Lisa
Culicchia, Frank
Lukiw, Walter J
Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title_full Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title_fullStr Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title_full_unstemmed Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title_short Neurofilament Light (NF-L) Chain Protein from a Highly Polymerized Structural Component of the Neuronal Cytoskeleton to a Neurodegenerative Disease Biomarker in the Periphery
title_sort neurofilament light (nf-l) chain protein from a highly polymerized structural component of the neuronal cytoskeleton to a neurodegenerative disease biomarker in the periphery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651065/
https://www.ncbi.nlm.nih.gov/pubmed/34881359
http://dx.doi.org/10.24966/AND-9608/100056
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