Neurofilament Phosphorylation during Development and Disease: Which Came First, the Phosphorylation or the Accumulation?

Dale, Jeffrey M.; Garcia, Michael L.

doi:10.1155/2012/382107

Cited by 49 publications

(45 citation statements)

References 95 publications

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“…124,125 It was expected that charge alterations induced by phosphorylation of these C-tails could play a role on controlling changes in the inter-filament spacing, the axonal caliber, and protein transport. 122,[126][127][128][129] This is because phosphorylation would increase electrostatic repulsion between the excess charges thereby promoting lateral extension of neurofilament tails. This hypothesis was proven to be wrong by a recent comprehensive analysis of physico-chemical and mechanical properties of phosphorylated and dephosphorylated composite filaments containing NF-L assembled with either NF-M (NF-LM), NF-H (NF-LH), or both (NF-LMH).…”

Section: 120mentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

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This article continues a series of short comments on the paradoxes and wonders of the protein intrinsic disorder phenomenon by introducing the "stability of instability" paradox. Intrinsically disordered proteins (IDPs) are characterized by the lack of stable 3D-structure, and, as a result, have an exceptional ability to sustain exposure to extremely harsh environmental conditions (an illustration of the "you cannot break what is already broken" principle). Extended IDPs are known to possess extreme thermal and acid stability and are able either to keep their functionality under these extreme conditions or to rapidly regain their functionality after returning to the normal conditions. Furthermore, sturdiness of intrinsic disorder and its capability to "ignore" harsh conditions provides some interesting and important advantages to its carriers, at the molecular (e.g., the cell wall-anchored accumulation-associated protein playing a crucial role in intercellular adhesion within the biofilm of Staphylococcus epidermidis), supramolecular (e.g., protein complexes, biologic liquid-liquid phase transitions, and proteinaceous membrane-less organelles), and organismal levels (e.g., the recently popularized case of the microscopic animals, tardigrades, or water bears, that use intrinsically disordered proteins to survive desiccation).

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Section: 120mentioning

confidence: 99%

Paradoxes and wonders of intrinsic disorder: Stability of instability

Uversky

2017

Intrinsically Disordered Proteins

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“…82 Stabilizing the axonal cytoskeleton The capacity of myelin to increase the calibre of axons through a mechanism involving neurofilaments has been known for many years. 76,83 The possibility that longterm axonal preservation depends on oligodendrogliamediated modification of the axonal cytoskeleton is suggested by the fact that degeneration of axons in MAG-null mice occurs on a background of reduced interneurofilament spacing, reduced neurofilament phosphorylation, 49,50 and possibly also microtubule instability. 65 The neuronal cytoskeletal stabilizing effects of myelin can be mediated directly by MAG-a process for which two major axonal receptor families have been identified: sialoglycans (particularly the gangliosides GD1a and GT1b) and members of the Nogo receptor (NgR) family.…”

Section: Metabolic Support For Axonsmentioning

confidence: 99%

Neuroprotection and repair in multiple sclerosis

et al. 2012

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Multiple sclerosis (MS) is an inflammatory demyelinating disease that is considered by many people to have an autoimmune aetiology. In recent years, new data emerging from histopathology, imaging and other studies have expanded our understanding of the disease and may change the way in which it is treated. Conceptual shifts have included: first, an appreciation of the extent to which the neuron and its axon are affected in MS, and second, elucidation of how the neurobiology of axon-glial and, particularly, axon-myelin interaction may influence disease progression. In this article, we review advances in both areas, focusing on the molecular mechanisms underlying axonal loss in acute inflammation and in chronic demyelination, and discussing how the restoration of myelin sheaths via the regenerative process of remyelination might prevent axon degeneration. An understanding of these processes could lead to better strategies for the prevention and treatment of axonal loss, which will ultimately benefit patients with MS.

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“…While its levels were unaffected by hypoxia in our cellular model, they were increased in all samples following reoxygenation, slightly more pronounced in the absence of Trx1. Neurofilament M is an intermediate filament protein that contributes to the maintenance of the neuronal phenotype [50]; GFAP is an intermediary filament protein that is specifically expressed in astrocytes [52]. Both the lack of Grx2 and Trx1 led to a significant reduction in neurofilament M levels compared to the control siRNA 20% O 2 group as well as the siGrx2 and siTrx1 20% O 2 groups.…”

Section: Discussionmentioning

confidence: 99%

“…Neurofilaments are proteins specifically expressed in neurons, where they stabilize the axon [49]. Neurofilaments M are intermediate filament proteins that play a key role in the maintenance of the neuronal phenotype [50]. GFAP is an intermediate filament protein specifically expressed in astroglia, the dominant and functionally most dynamic glial cell type [51,52].…”

Section: The Importance and Effects Of Trx1 And Grx2 In A Cellular Momentioning

confidence: 99%