Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of motoneuron disease
Open accessAbstract
Apoptosis is a hallmark of motoneuron diseases such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) [1]. In a widely used mouse model of motoneuron disease (progressive motor neuronopathy or pmn) [2-4], transgenic expression of the anti-apoptotic bcl-2 gene [5] or treatment with glial cell-derived neurotrophic factor [6] prevents the apoptosis of the motoneuron soma; however, they were unable to affect the life span of the animals. The goal of the present work was to determine whether the pmn phenotype could be rescued by means of a gene that inhibits axon degeneration. For this reason, the pmn mice were crossed with mice bearing the dominant Wlds ("slow Wallerian degeneration") mutation, which slows axon degeneration and synapse loss [7-9]. We show here that the Wlds gene product attenuates symptoms, extends life span, prevents axon degeneration, rescues motoneuron number and size, and delays retrograde transport deficits in pmn/pmn mice. These results suggest new pathogenic mechanisms and therapeutic avenues for motoneuron diseases.
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Inhibition of synaptic loss reduces apoptosis of motor neurons in a mouse model of motor neuron disease.
“inhibition of synaptic loss reduces apoptosis of motor neurons in a mouse model of motor neuron disease (37).”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [37]
The same mitochondrial-induced initiation of apoptosis signaling that occurs in skeletal muscle also occurs in neuromuscular junctions with aging.
“Together, these observations confirm that the same mitochondrial-induced initiation of apoptosis signaling that occurs in skeletal muscle also occurs in neuromuscular junctions with aging.”
From Mitochondria initiate and regulate sarcopenia (2017) · cites this paper as [37]
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“For example, the progressive motor neuronopathy (pmn) mouse, which undergoes massive motor axon loss in the first weeks after weaning due to deficiency of a key protein for microtubule formation and axonal transport [38], has motor neuron loss that follows slightly after axon loss [39].”
BackgroundResultInfluentialSelf-citation
- Authors
- Ferri, A., Sanes, J. R., Coleman, M. P., Cunningham, J. M., & Kato, A. C.
- Affiliations
- University of Geneva (CH)
- Washington University in St. Louis (US)
- University of Cologne (DE)
- Corresponding author
- Kato, Ann C.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 13
- Issue
- 8
- Pages
- 669-673
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2037770052
- Cited by
- 221
- References
- 21
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 12 · 2012: 9
- FWCI
- 9.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3760 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Keywords
- motor neuron disease, axonal degeneration, synaptic loss, apoptosis, amyotrophic lateral sclerosis, spinal muscular atrophy, retrograde transport, disease progression, lifespan extension, transgenic rescue
- MeSH terms
- Animals, Axons, Crosses, Genetic, Disease Models, Animal, Mice, Transgenic, Nerve Tissue Proteins, Neuromuscular Junction, Staining and Labeling, Synapses, Motor Neuron Disease, Apoptosis, Mice
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