Retrograde axonal transport of neurotrophins: Differences between neuronal populations and implications for motor neuron disease

1998 ◽  
Vol 76 (5) ◽  
pp. 419-423 ◽  
Author(s):  
Selena E Bartlett ◽  
Anna J Reynolds ◽  
Ian A Hendry
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Axonal Transport ◽  
Retrograde Axonal Transport ◽  
Neuronal Populations

Impairment of retrograde axonal transport in wobbler mouse motor neuron disease

1990 ◽  
Vol 13 (2) ◽  
pp. 121-126 ◽  
Author(s):  
Hiroshi Mitsumoto ◽  
Anita L. Ferut ◽  
Kozo Kurahashi ◽  
Irvine G. McQuarrie
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Axonal Transport ◽  
Retrograde Axonal Transport ◽  
Wobbler Mouse

scholarly journals Retrograde axonal transport and motor neuron disease

2008 ◽  
Vol 106 (2) ◽  
pp. 495-505 ◽  
Author(s):  
Anna-Lena Strm ◽  
Jozsef Gal ◽  
Ping Shi ◽  
Edward J. Kasarskis ◽  
Lawrence J. Hayward ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Axonal Transport ◽  
Retrograde Axonal Transport

scholarly journals Contemporary Circulating Enterovirus D68 Strains Infect and Undergo Retrograde Axonal Transport in Spinal Motor Neurons Independent of Sialic Acid

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Alison M. Hixon ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Sialic Acid ◽  
Motor Neuron ◽  
Axonal Transport ◽  
Motor Neurons ◽  
The United States ◽  
Retrograde Axonal Transport ◽  
Spinal Motor Neurons ◽  
Acute Flaccid Myelitis ◽  
Spinal Motor ◽  
Enterovirus D68

ABSTRACTEnterovirus D68 (EV-D68) is an emerging virus that has been identified as a cause of recent outbreaks of acute flaccid myelitis (AFM), a poliomyelitis-like spinal cord syndrome that can result in permanent paralysis and disability. In experimental mouse models, EV-D68 spreads to, infects, and kills spinal motor neurons following infection by various routes of inoculation. The topography of virus-induced motor neuron loss correlates with the pattern of paralysis. The mechanism(s) by which EV-D68 spreads to target motor neurons remains unclear. We sought to determine the capacity of EV-D68 to spread by the neuronal route and to determine the role of known EV-D68 receptors, sialic acid and intracellular adhesion molecule 5 (ICAM-5), in neuronal infection. To do this, we utilized a microfluidic chamber culture system in which human induced pluripotent stem cell (iPSC) motor neuron cell bodies and axons can be compartmentalized for independent experimental manipulation. We found that EV-D68 can infect motor neurons via their distal axons and spread by retrograde axonal transport to the neuronal cell bodies. Virus was not released from the axons via anterograde axonal transport after infection of the cell bodies. Prototypic strains of EV-D68 depended on sialic acid for axonal infection and transport, while contemporary circulating strains isolated during the 2014 EV-D68 outbreak did not. The pattern of infection did not correspond with the ICAM-5 distribution and expression in either human tissue, the mouse model, or the iPSC motor neurons.IMPORTANCEEnterovirus D68 (EV-D68) infections are on the rise worldwide. Since 2014, the United States has experienced biennial spikes in EV-D68-associated acute flaccid myelitis (AFM) that have left hundreds of children paralyzed. Much remains to be learned about the pathogenesis of EV-D68 in the central nervous system (CNS). Herein we investigated the mechanisms of EV-D68 CNS invasion through neuronal pathways. A better understanding of EV-D68 infection in experimental models may allow for better prevention and treatment strategies of EV-D68 CNS disease.

scholarly journals Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors

2019 ◽  
Author(s):  
Kyoko Chiba ◽  
Chen Min ◽  
Shogo Arai ◽  
Koichi Hashimoto ◽  
Richard J. McKenney ◽  
...  
Keyword(s):  
Motor Activity ◽  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Synaptic Vesicle ◽  
Axonal Transport ◽  
Cell Biology ◽  
Neuronal Morphology ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Anterograde Axonal Transport

AbstractKIF1A is a kinesin-family motor involved in the axonal transport of synaptic vesicle precursors (SVPs) along microtubules. In humans, more than ten point mutations in KIF1A are associated with the motor neuron disease, hereditary spastic paraplegia (SPG). However, not all of these mutations appear to inhibit the motility of the KIF1A motor, and thus, a clear molecular explanation for how KIF1A mutations lead to neuropathy is not available. In this study, we established in vitro motility assays with purified full-length human KIF1A and found that KIF1A mutations associated with the pure form of spastic paraplegia hyperactivate motility of the KIF1A motor. Introduction of the corresponding mutations into Caenorhabditis elegans KIF1A homologue unc-104 revealed abnormal accumulation of SVPs at the tips of axons and increased anterograde axonal transport of SVPs. Our data reveal that hyper-activation of kinesin motor activity, rather than its loss-of-function, is a novel cause of motor neuron disease in humans.Significance StatementAnterograde axonal transport supplies organelles and protein complexes throughout axonal processes to support neuronal morphology and function. It has been observed that reduced anterograde axonal transport is associated with neuronal diseases. In contrast, here we show that particular disease-associated mutations in KIF1A, an anterograde axonal motor for synaptic vesicle precursors, induce hyperactivation of KIF1A motor activity and increased axonal transport of synaptic vesicle precursors. Our results advance the knowledge of the regulation of motor proteins and axonal transport and cell biology of motor neuron diseases.

Widespread loss of neuronal populations in the spinal ventral horn in sporadic motor neuron disease. A morphometric study

2006 ◽  
Vol 244 (1-2) ◽  
pp. 41-58 ◽  
Author(s):  
Benjamin Stephens ◽  
Roberto J. Guiloff ◽  
Roberto Navarrete ◽  
Piers Newman ◽  
Nirjal Nikhar ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Ventral Horn ◽  
Morphometric Study ◽  
Neuronal Populations ◽  
Sporadic Motor Neuron Disease

scholarly journals Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors

2019 ◽  
Vol 116 (37) ◽  
pp. 18429-18434 ◽  
Author(s):  
Kyoko Chiba ◽  
Hironori Takahashi ◽  
Min Chen ◽  
Hiroyuki Obinata ◽  
Shogo Arai ◽  
...  
Keyword(s):  
Motor Neuron ◽  
Motor Neuron Disease ◽  
Synaptic Vesicle ◽  
Axonal Transport ◽  
Point Mutations ◽  
Loss Of Function ◽  
In Vitro Motility ◽  
Anterograde Axonal Transport ◽  
Abnormal Accumulation

KIF1A is a kinesin family motor involved in the axonal transport of synaptic vesicle precursors (SVPs) along microtubules (MTs). In humans, more than 10 point mutations inKIF1Aare associated with the motor neuron disease hereditary spastic paraplegia (SPG). However, not all of these mutations appear to inhibit the motility of the KIF1A motor, and thus a cogent molecular explanation for howKIF1Amutations lead to neuropathy is not available. In this study, we established in vitro motility assays with purified full-length human KIF1A and found thatKIF1Amutations associated with the hereditary SPG lead to hyperactivation of KIF1A motility. Introduction of the corresponding mutations into theCaenorhabditis elegans KIF1Ahomologunc-104revealed abnormal accumulation of SVPs at the tips of axons and increased anterograde axonal transport of SVPs. Our data reveal that hyperactivation of kinesin motor activity, rather than its loss of function, is a cause of motor neuron disease in humans.

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