WordNet

cause to flow; "The artist flowed the washes on the paper"
the amount of fluid that flows in a given time (同)flow_rate, rate of flow
any uninterrupted stream or discharge
cover or swamp with water
the act of flowing or streaming; continuous progression (同)stream
the motion characteristic of fluids (liquids or gases) (同)flowing
move or progress freely as if in a stream; "The crowd flowed out of the stadium" (同)flux
be abundantly present; "The champagne flowed at the wedding"

PrepTutorEJDIC

《副詞巳句始を伴って》〈気体・液体・電気などが〉『流れる』 / 《副詞[句]を伴って》〈言葉・人々などず〉流れるように続く / 〈心・場所などが〉(…で)いっぱいになる,満ちあふれる《+『with』+『名』》 / 《副詞[句]を伴って》〈髪・服などが〉長く垂れる;風になびく / 〈潮が〉満ちる / (…から)生じる,発生する《+『from』+『名』》 / 〈C〉《単数形で》(気体・液体・電気などの)『流れ』《+『of』+『名』》 / 〈C〉《単数形で》(言葉・人などの)絶え間のない(よどみのない)流れ《+『of』+『名』》 / 〈C〉《単数形で》(…の)洪水,はんらん《+『of』+『名』》 / 〈U〉《the flow》満ち潮,上げ潮
流れる / 流ちょうな / ゆるやにかに垂れた

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/01 15:44:01」(JST)

wiki en

Dynein, a motor protein responsible for retrograde axonal transport, carries vesicles and other cellular products toward the cell bodies of neurons. Its light chains bind the cargo, and its globular head regions bind the microtubule, "inching" along it.

Axoplasmic transport, also called axonal transport, is a cellular process responsible for movement of mitochondria, lipids, synaptic vesicles, proteins, and other cell parts (i.e. organelles) to and from a neuron's cell body, through the cytoplasm of its axon (the axoplasm). Axons, which can be 1,000 or 10,000 times the length of the cell body, were originally thought not to contain any ribosomes as the means of producing proteins, and so were thought to rely on axoplasmic transport for all their protein needs.^[1]^[2] However, more recently, mRNA translation has been demonstrated in axons.^[3]^[4] Axonal transport is also responsible for moving molecules destined for degradation from the axon back to the cell body, where they are broken down by lysosomes.^[5]

Movement toward the cell body is called retrograde transport and movement toward the synapse is called anterograde transport.^[1]^[6]^[7]

Mechanism

The vast majority of axonal proteins are synthesized in the neuronal cell body and transported along axons. Axonal transport occurs throughout the life of a neuron and is essential to its growth and survival. Microtubules (made of tubulin) run along the length of the axon and provide the main cytoskeletal "tracks" for transportation. Kinesin and dynein are motor proteins that move cargoes in the anterograde (forwards from the soma to the axon tip) and retrograde (backwards to the soma (cell body)) directions, respectively. Motor proteins bind and transport several different cargoes including mitochondria, cytoskeletal polymers, and synaptic vesicles containing neurotransmitters.^[1]

Axonal transport can be fast or slow, and anterograde or retrograde.

Fast and slow transport

Vesicular cargoes move relatively fast (50–400 mm/day) whereas transport of soluble (cytosolic) and cytoskeletal proteins takes much longer (moving at less than 8 mm/day). The basic mechanism of fast axonal transport has been understood for decades but the mechanism of slow axonal transport is only recently becoming clear, as a result of advanced imaging techniques.^[8] Fluorescent labeling techniques (e.g. fluorescence microscopy) have enabled direct visualization of transport in living neurons. (See also: Anterograde tracing.)

Recent studies have revealed that the movement of cytoskeletal "slow" cargoes is actually rapid but unlike fast cargoes, they pause frequently, making the overall transit rate much slower. The mechanism is known as the "Stop and Go" model of slow axonal transport, and has been extensively validated for the transport of the cytoskeletal protein neurofilament.^[9] The movement of soluble (cytosolic) cargoes is more complex, but appears to have a similar basis where soluble proteins organize into multi-protein complexes that are then conveyed by transient interactions with more rapidly moving cargoes moving in fast axonal transport ^[10]^[11]^[12] An analogy is the difference in transport rates between local and express subway trains. Though both types of train travel at similar velocities between stations, the local train takes much longer to reach the end of the line because it stops at every station whereas the express makes only a few stops on the way.

Anterograde transport

Anterograde (also called "orthograde") transport is movement of molecules/organelles outward, from the cell body (also called soma) to the synapse or cell membrane.

The anterograde movement of individual cargoes (in transport vesicles) of both fast and slow components along the microtubule^[7] is mediated by kinesins. Several kinesins have been implicated in slow transport,^[8] though the mechanism for generating the "pauses" in the transit of slow component cargoes is still unknown.

There are two classes of slow anterograde transport: slow component a (SCa) that carries mainly microtubules and neurofilaments at 0.1-1 millimeters per day, and slow component b (SCb) that carries over 200 diverse proteins and actin at a rate of up to 6 millimeters per day.^[8] The slow component b, which also carries actin, are transported at a rate of 2-3 millimeters per day in retinal cell axons.

During reactivation from latency, the herpes simplex virus (HSV) enters its lytic cycle, and uses anterograde transport mechanisms to migrate from dorsal root ganglia neurons to the skin or mucosa that it subsequently affects.^[13]

Retrograde transport

Retrograde transport is movement of molecules/organelles inward, away from the synapse or plasma membrane toward the cell body or soma. Retrograde transport is mediated by dynein, and is used for example to send chemical messages and endocytosis products headed to endolysosomes from the axon back to the cell.^[5] Fast retrograde transport can cover 100-200 millimeters per day.^[5]

Fast retrograde transport returns used synaptic vesicles and other materials to the soma and informs the soma of conditions at the axon terminals. Some pathogens exploit this process to invade the nervous system. They enter the distal tips on an axon and travel to the soma by retrograde transport. Examples include tetanus toxin and the herpes simplex, rabies, and polio viruses. In such infections, the delay between infection and the onset of symptoms corresponds to the time needed for the pathogens to reach the somas.^[14]

Consequences of interruption

Several rare neurodegenerative diseases are linked to genetic mutations in the motor proteins, kinesin and dynein, and in those cases it is likely that axonal transport is a key player in mediating pathology. Dysfunctional axonal transport is also linked to sporadic (common) forms of neurodegenerative diseases such as Alzheimer's and Parkinson's.^[8] This is mainly due to numerous observations that large axonal accumulations are invariably seen in affected neurons, and that genes known to play a role in the familial forms of these diseases also have purported roles in normal axonal transport. However there is little direct evidence for involvement of axonal transport in the latter diseases, and other mechanisms (such as direct synaptotoxicity) may be more relevant.

Since the axon depends on axoplasmic transport for vital proteins and materials, injury such as diffuse axonal injury that interrupts the transport will cause the distal axon to degenerate in a process called Wallerian degeneration. Cancer drugs that interfere with cancerous growth by altering microtubules (which are necessary for cell division) damage nerves because the microtubules are necessary for axonal transport.^[1]

Infection

The rabies virus reaches the central nervous system by retrograde axoplasmic flow.^[15]

References

^ ^a ^b ^c ^d Cowie R.J. and Stanton G.B. "Axoplasmic Transport and Neuronal Responses to Injury." Howard University College of Medicine. Retrieved on January 25, 2007.
^ Sabry J., O’Connor T. P., and Kirschner M. W. 1995. Axonal Transport of Tubulin in Ti1 Pioneer Neurons in Situ. Neuron. 14(6): 1247-1256. PMID 7541635. Retrieved on January 25, 2007.
^ Giustetto M, Hegde AN, Si K, et al. Axonal transport of eukaryotic translation elongation factor 1alpha mRNA couples transcription in the nucleus to long-term facilitation at the synapse. Proc Natl Acad Sci. 2003 Nov 11;100(23):13680-5. Epub 2003 Oct 24. PMID 14578450.
^ Si K, Giustetto M, Etkin A, et al. A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia.Cell. 2003 Dec 26;115(7):893-904. PMID 14697206.
^ ^a ^b ^c Oztas E. 2003. Neuronal Tracing. (PDF) Neuroanatomy. 2: 2-5.
^ Karp G. 2005. Cell and Molecular Biology: Concepts and Experiments, Fourth ed, p. 344. John Wiley and Sons, Hoboken, NJ. ISBN 0-471-46580-1
^ ^a ^b Bear et al., 2006. "Neuroscience: Exploring the Brain," 3/e, p. 41
^ ^a ^b ^c ^d Roy S, et al. 2005. Axonal transport defects: a common theme in neurodegenerative Acta Neuropathol 109: 5-13. PMID 15645263.
^ Brown 2003. "Axonal transport of membranous and nonmembranous cargoes: a unified perspective", J Cell Biol. 2003 Mar 17;160(6):817-21
^ Scott et al., 2011. Mechanistic logic underlying the axonal transport of cytosolic proteins". Neuron. 2011 May 12;70(3):441-54.
^ Roy S et al., 2007. "Rapid and intermittent cotransport of slow component-b proteins". J Neurosci. 2007 Mar 21;27(12):3131-8
^ Kuznetsov, Andrey V. (2011). "Analytical solution of equations describing slow axonal transport based on the stop-and-go hypothesis". Central European Journal of Physics 9 (3): 662–673. doi:10.2478/s11534-010-0066-0.
^ Holland, David J. , Monica Miranda-Saksena, et al. "Anterograde Transport of Herpes Simplex Virus Proteins in Axons of Peripheral Human Fetal Neurons: an Immunoelectron Microscopy Study." Journal of Virology . 73.10 (1999): 8503-8511. Web. 6 Dec. 2011. <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC112870/>.
^ Saladin, Kenneth. Anatomy and Physiology: The Unity of Form and Function. Sixth. New York : McGraw-Hill, 2010. 445. Print.
^ Mitrabhakdi E, Shuangshoti S, Wannakrairot P, Lewis RA, Susuki K, et al. (2005) Differences in neuropathogenetic mechanisms in human furious and paralytic rabies. J Neurol Sci 238: 3-10.PMID 16226769

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 冠動脈圧およびドップラー血流測定の臨床使用 clinical use of coronary artery pressure and doppler flow measurements
2. 冠側副循環 coronary collateral circulation
3. 非動脈炎性前部虚血性視神経症：疫学、発症機序、および病因 nonarteritic anterior ischemic optic neuropathy epidemiology pathogenesis and etiologies
4. 非動脈炎性虚血性視神経症：予後および治療 nonarteritic ischemic optic neuropathy prognosis and treatment
5. 単純ヘルペス性角膜炎 herpes simplex keratitis

English Journal

Nose-to-brain transport of aerosolised quantum dots following acute exposure.

Hopkins LE1, Patchin ES, Chiu PL, Brandenberger C, Smiley-Jewell S, Pinkerton KE.
Nanotoxicology.Nanotoxicology.2014 Dec;8(8):885-93. doi: 10.3109/17435390.2013.842267.
Nanoparticles are of wide interest due to their potential use for diverse commercial applications. Quantum dots (QDs) are semiconductor nanocrystals possessing unique optical and electrical properties. Although QDs are commonly made of cadmium, a metal known to have neurological effects, potential t
PMID 24040866

Adapting brain metabolism to myelination and long-range signal transduction.

Hirrlinger J1, Nave KA.
Glia.Glia.2014 Nov;62(11):1749-61. doi: 10.1002/glia.22737. Epub 2014 Aug 6.
In the mammalian brain, the subcortical white matter comprises long-range axonal projections and their associated glial cells. Here, astrocytes and oligodendrocytes serve specific functions during development and throughout adult life, when they meet the metabolic needs of long fiber tracts. Within
PMID 25130164

C9orf72 FTLD/ALS-associated Gly-Ala dipeptide repeat proteins cause neuronal toxicity and Unc119 sequestration.

May S1, Hornburg D, Schludi MH, Arzberger T, Rentzsch K, Schwenk BM, Grässer FA, Mori K, Kremmer E, Banzhaf-Strathmann J, Mann M, Meissner F, Edbauer D.
Acta neuropathologica.Acta Neuropathol.2014 Oct;128(4):485-503. doi: 10.1007/s00401-014-1329-4. Epub 2014 Aug 14.
Hexanucleotide repeat expansion in C9orf72 is the most common pathogenic mutation in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the lack of an ATG start codon, the repeat expansion is translated in all reading frames into dipeptide repeat
PMID 25120191

Japanese Journal

手根管症候群の診断のピットフォール : 手根管症候群の症状はいわゆる正中神経領域だけではない

姜良勲,佐々木康介,寺浦英俊,五谷寛之,坂中秀樹,山野慶樹,三澤弘道
末梢神経 = Peripheral nerve 19(2), 410-412, 2008-12-01
NAID 10025625706

Secretion of Bax-Like Protein into Systemic Circulation from the Posterior Pituitary in the Rat Hypothalamo-Posterior Pituitary System

Matsuda Tomoyuki,Tamada Yoshitaka,Hayashi Seiji,Iijima Norio,Tanaka Masaki,Yamada Hisao,Utsunomiya Kazuhiro,Kudo Motoi,Kurokawa Kiyoshi,Kataoka Kiyoshi,yanaihara Noboru,Nagasawa Shingo,Ibata Yasuhiko
Acta histochemica et cytochemica 34(2), 119-128, 2001
… From these results, Bax-like protein is considered to be produced in the hypothalamic oxytocin neurons, transported through axoplasmic flow and secreted into systemic circulation at the posterior pituitary as a "neurohormone". …
NAID 110003150829