Neurofilaments at a glance

Yuan, Ao; Rao, M. Subba; Veeranna,; Nixon, Ralph A.

doi:10.1242/jcs.104729

Cited by 349 publications

(282 citation statements)

References 135 publications

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“…Mammalian neurofilaments consist of three subunits, termed NF-H, NF-M and NF-L (corresponding to heavy, medium and light, according to their molecular mass) (Nixon and Shea, 1992;Pant and Veeranna, 1995), along with a-internexin and peripherin (Yuan et al, 2006;Yuan et al, 2012). NF-H and NF-M Cterminal phosphorylation fosters divalent-cation-dependent neurofilament-neurofilament interactions that mediate the formation of the stationary cytoskeleton, which provides support to the axon (Nixon, 1998;Yabe et al, 2001b;Shea and Lee, 2011;Shea and Lee, 2013).…”

Section: Introductionmentioning

confidence: 99%

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Lee

Pant²,

Shea

2014

Journal of Cell Science

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C-terminal neurofilament phosphorylation mediates cation-dependent self-association leading to neurofilament incorporation into the stationary axonal cytoskeleton. Multiple kinases phosphorylate the C-terminal domains of the heavy neurofilament subunit (NF-H), including cyclin-dependent protein kinase 5 (CDK5), mitogenactivated protein kinases (MAPKs), casein kinase 1 and 2 (CK1 and CK2) and glycogen synthase kinase 3b (GSK3b). The respective contributions of these kinases have been confounded because they phosphorylate multiple substrates in addition to neurofilaments and display extensive interaction. Herein, differentiated NB2a/d1 cells were transfected with constructs expressing GFP-tagged NF-H, isolated NF-H sidearms and NF-H lacking the distal-most 187 amino acids. Cultures were treated with roscovitine, PD98059, Li + , D4476, tetrabromobenzotriazole and calyculin, which are active against CDK5, MKK1 (also known as MAP2K1), GSK3b, CK1, CK2 and protein phosphatase 1 (PP1), respectively. Sequential phosphorylation by CDK5 and GSK3b mediated the neurofilamentneurofilament associations. The MAPK pathway (i.e. MKK1 to ERK1/ 2) was found to downregulate GSK3b, and CK1 activated PP1, both of which promoted axonal transport and restricted neurofilamentneurofilament associations to axonal neurites. The MAPK pathway and CDK5, but not CK1 and GSK3b, inhibited neurofilament proteolysis. These findings indicate that phosphorylation of neurofilaments by the proline-directed MAPK pathway and CDK5 counterbalance the impact of phosphorylation of neurofilaments by the non-proline-directed CK1 and GSK3b.

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Section: Introductionmentioning

confidence: 99%

Divergent and convergent roles for kinases and phosphatases in neurofilament dynamics

Lee

Pant²,

Shea

2014

Journal of Cell Science

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“…The expression of neurofilaments and their degree of phosphorylation (dephosphorylation increases the sensitivity of neurofilaments to enzymatic degradation involving calpains) can also be z udziałem kalpain) może być zmieniona w chorobach mózgu (zapalnych i neurodegeneracyjnych, takich jak np. stwardnienie rozsiane czy choroba Alzheimera), dlatego istotne jest szczegółowe zapoznanie się z dokumentacją medyczną zmarłego, jeśli takowa jest dostępna [5,7,23,33].…”

Section: Factors Determining the Results Of Neuroimmunochemical Analysisunclassified

“…Therefore, it is absolutely vital to thoroughly examine the dead patient's medical records, if they are available [5,7,23,33].…”

Section: Autorzy Deklarują Brak Konfliktu Interesówmentioning

confidence: 99%

Neurofilaments and traumatic brain injury

Kobek¹,

Skowronek²,

Jankowski³

et al. 2014

amsik

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StreszczenieW neurotraumatologii medyczno-sądowej praktyczne znaczenie ma obiektywne ustalenie wieku -czasu powstania stłuczenia mózgu. Obecnie postęp immunohistochemii umożliwia badania elementów strukturalnych komórek, w tym także białek cytoszkieletu neuronu -neurofilamentów, które ze względu na swoje właściwości mogłyby zostać wykorzystane do określania wieku obrażeń mózgu w medycynie sądowej. Celem niniejszej pracy jest przegląd aktualnego piśmiennictwa pod kątem badań dotyczących zmian zachodzących w neurofilamentach po urazie mózgu, zarówno w modelach zwierzęcych, jak i w ludzkim materiale biologicznym. Przegląd wykazał brak danych dotyczących czasowych zmian struktury neurofilamentów po urazie mózgu u ludzi, które mogłyby zostać wykorzystane do określania wieku obrażeń w medycynie sądowej.Słowa kluczowe: neurostruktura, neurofilamenty, urazowe uszkodzenie mózgu, medycyna sądowa, immunohistochemia. AbstractObjective determination of the time of brain contusion is of key importance in medicolegal neurotraumatology. Currently, the progress of immunohistochemistry allows the study of structural elements of cells including neurofilaments, i.e. neuronal cytoskeletal proteins possessing properties that could be used for determining the age of brain injury in forensic medicine. The purpose of this study was to review recently published literature with a focus on studies investigating changes which occur in neurofilaments after brain trauma, both in animal models and in human biological material. The review has shown a lack of data on temporal changes in neurofilament expression after human brain trauma which could be used for determining the age of injuries in forensic medicine.

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“…Lactate level has been shown to be associated with mortality in trauma, burns, sepsis and ROSC after cardiac arrest [8][9][10][11]. NfH belongs to the intermediate filaments class, are abundant in axons and are present in both central and peripheral nervous system, playing a central role in axon growing [12]. Increased serum levels of NfH have been reported in states associated with neuronal injury [13][14], and it has been proposed as surrogate markers of brain injury after cardiac arrest [15].…”

Section: Introductionmentioning

confidence: 99%