Axonal transport and amyotrophic lateral sclerosis

2021 ◽  
pp. 309-321
Author(s):  
Andy Grierson ◽  
Chris Miller
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Lateral Sclerosis

Defective axonal transport in a transgenic mouse model of amyotrophic lateral sclerosis

Nature ◽  
1995 ◽  
Vol 375 (6526) ◽  
pp. 61-64 ◽  
Author(s):  
Jean-François Collard ◽  
Francine Côté ◽  
Jean-Pierre Julien
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Axonal Transport ◽  
Transgenic Mouse Model ◽  
Lateral Sclerosis

scholarly journals Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content

2007 ◽  
Vol 16 (22) ◽  
pp. 2720-2728 ◽  
Author(s):  
Kurt J. De Vos ◽  
Anna L. Chapman ◽  
Maria E. Tennant ◽  
Catherine Manser ◽  
Elizabeth L. Tudor ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Familial Amyotrophic Lateral Sclerosis ◽  
Fast Axonal Transport ◽  
Lateral Sclerosis

scholarly journals Neurofilaments and Orthograde Transport Are Reduced in Ventral Root Axons of Transgenic Mice that Express Human SOD1 with a G93A Mutation

1997 ◽  
Vol 139 (5) ◽  
pp. 1307-1315 ◽  
Author(s):  
Bin Zhang ◽  
Pang-hsien Tu ◽  
Farhad Abtahian ◽  
John Q. Trojanowski ◽  
Virginia M.-Y. Lee
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Axonal Transport ◽  
Motor Neurons ◽  
Temporal Correlation ◽  
Motor Weakness ◽  
Concomitant Reduction ◽  
Ventral Roots ◽  
Human Sod1 ◽  
Lateral Sclerosis

Mice engineered to express a transgene encoding a human Cu/Zn superoxide dismutase (SOD1) with a Gly93 → Ala (G93A) mutation found in patients who succumb to familial amyotrophic lateral sclerosis (FALS) develop a rapidly progressive and fatal motor neuron disease (MND) similar to amyotrophic lateral sclerosis (ALS). Hallmark ALS lesions such as fragmentation of the Golgi apparatus and neurofilament (NF)-rich inclusions in surviving spinal cord motor neurons as well as the selective degeneration of this population of neurons were also observed in these animals. Since the mechanism whereby mutations in SOD1 lead to MND remains enigmatic, we asked whether NF inclusions in motor neurons compromise axonal transport during the onset and progression of MND in a line of mice that contained ∼30% fewer copies of the transgene than the original G93A (Gurney et al., 1994). The onset of MND was delayed in these mice compared to the original G93A mice, but they developed the same neuropathologic abnormalities seen in the original G93A mice, albeit at a later time point with fewer vacuoles and more NF inclusions. Quantitative Western blot analyses showed a progressive decrease in the level of NF proteins in the L5 ventral roots of G93A mice and a concomitant reduction in axon caliber with the onset of motor weakness. By ∼200 d, both fast and slow axonal transports were impaired in the ventral roots of these mice coincidental with the appearance of NF inclusions and vacuoles in the axons and perikarya of vulnerable motor neurons. This is the first demonstration of impaired axonal transport in a mouse model of ALS, and we infer that similar impairments occur in authentic ALS. Based on the temporal correlation of these impairments with the onset of motor weakness and the appearance of NF inclusions and vacuoles in vulnerable motor neurons, the latter lesions may be the proximal cause of motor neuron dysfunction and degeneration in the G93A mice and in FALS patients with SOD1 mutations.

scholarly journals Amyotrophic lateral sclerosis-associated mutant VAPBP56S perturbs calcium homeostasis to disrupt axonal transport of mitochondria

2012 ◽  
Vol 21 (9) ◽  
pp. 1979-1988 ◽  
Author(s):  
G. M. Morotz ◽  
K. J. De Vos ◽  
A. Vagnoni ◽  
S. Ackerley ◽  
C. E. Shaw ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Calcium Homeostasis ◽  
Lateral Sclerosis

scholarly journals Amyotrophic lateral sclerosis-associated mutant SOD1 inhibits anterograde axonal transport of mitochondria by reducing Miro1 levels

2017 ◽  
Vol 26 (23) ◽  
pp. 4668-4679 ◽  
Author(s):  
Annekathrin Moller ◽  
Claudia S Bauer ◽  
Rebecca N Cohen ◽  
Christopher P Webster ◽  
Kurt J De Vos
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Mutant Sod1 ◽  
Anterograde Axonal Transport ◽  
Lateral Sclerosis

scholarly journals Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis

2012 ◽  
Vol 109 (11) ◽  
pp. 4296-4301 ◽  
Author(s):  
P. Marinkovic ◽  
M. S. Reuter ◽  
M. S. Brill ◽  
L. Godinho ◽  
M. Kerschensteiner ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Mouse Models ◽  
Lateral Sclerosis

scholarly journals BDNF-dependent modulation of axonal transport is selectively impaired in ALS

2021 ◽  
Author(s):  
Andrew P. Tosolini ◽  
James N. Sleigh ◽  
Sunaina Surana ◽  
Elena R. Rhymes ◽  
Stephen D. Cahalan ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Axonal Transport ◽  
Neuronal Development ◽  
Therapeutic Interventions ◽  
Wild Type ◽  
Disease Pathogenesis ◽  
Sciatic Nerves ◽  
Lateral Sclerosis ◽  
Selective Impairment ◽  
Stimulation Of

AbstractAxonal transport ensures long-range delivery of essential cargoes between proximal and distal compartments of neurons, and is needed for neuronal development, function, and survival. Deficits in axonal transport have been detected at pre-symptomatic stages in mouse models of amyotrophic lateral sclerosis (ALS), suggesting that impairments are fundamental for disease pathogenesis. However, the precise mechanisms responsible for the transport deficits and whether they preferentially affect α-motor neuron (MN) subtypes remain unresolved. Here, we report that stimulation of wild-type neurons with brain-derived neurotrophic factor (BDNF) enhances trafficking of signalling endosomes specifically in fast MNs (FMNs). In early symptomatic SOD1G93A mice, FMNs display selective impairment of axonal transport and develop an insensitivity to BDNF stimulation, with pathology upregulating classical non-pro-survival receptors in muscles and sciatic nerves. Altogether, these data indicate that cell- and non-cell autonomous BDNF signalling is impaired in vulnerable SOD1G93A MNs, thus identifying a new key deficit in ALS amenable for future therapeutic interventions.

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