Prion-like propagation of mutant SOD1 misfolding and motor neuron disease spread along neuroanatomical pathways

Abstract A hallmark feature of amyotrophic lateral sclerosis (ALS) is that symptoms appear to spread along neuroanatomical pathways to engulf the motor nervous system, suggesting a propagative toxic entity could be involved in disease pathogenesis. Evidence for such a propagative entity emerged recently in studies using mice that express G85R-SOD1 mutant protein fused to YFP (G85R-SOD1:YFP). Heterozygous G85R-SOD1:YFP transgenic mice do not develop ALS symptoms out to 20 months of age. However, when newborns are injected with spinal homogenates from paralyzed mutant SOD1 mice, the G85R-SOD1:YFP mice develop paralysis as early as 6 months of age. We now demonstrate that injecting spinal homogenates from paralyzed mutant SOD1 mice into the sciatic nerves of adult G85R-SOD1:YFP mice produces a spreading motor neuron disease within 3.0 ± 0.2 months of injection. The formation of G85R-SOD1:YFP inclusion pathology spreads slowly in this model system; first appearing in the ipsilateral DRG, then lumbar spinal cord, before spreading rostrally up to the cervical cord by the time mice develop paralysis. Reactive astrogliosis mirrors the spread of inclusion pathology and motor neuron loss is most severe in lumbar cord. G85R-SOD1:YFP inclusion pathology quickly spreads to discrete neurons in the brainstem and midbrain that are synaptically connected to spinal neurons, suggesting a trans-synaptic propagation of misfolded protein. Taken together, th...
Source: Acta Neuropathologica - Category: Neurology Source Type: research

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Conclusions This study demonstrates that cerebral degeneration in ALS is more pronounced in the motor than prefrontal cortex, that multicenter MRS studies are feasible, and that motor tNAA/Ino shows promise as a potential biomarker.
Source: Neurology Clinical Practice - Category: Neurology Authors: Tags: MRI, MRS, Amyotrophic lateral sclerosis Research Source Type: research
Authors: Valori CF, Guidotti G, Brambilla L, Rossi D Abstract Motor neuron disorders are highly debilitating and mostly fatal conditions for which only limited therapeutic options are available. To overcome this limitation and develop more effective therapeutic strategies, it is critical to discover the pathogenic mechanisms that trigger and sustain motor neuron degeneration with the greatest accuracy and detail. In the case of Amyotrophic Lateral Sclerosis (ALS), several genes have been associated with familial forms of the disease, whilst the vast majority of cases develop sporadically and no defined cause can be...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
People living with amyotrophic lateral sclerosis (ALS) and their families were provided with equitable open access to a new dedicated psychology service. An integrative psychotherapeutic model of support was offered, incorporating existential therapy. The therapeutic potential of existential therapy, which was evident here, has not been explored previously in ALS. Cognitive behavioural interventions were used in a minority of cases. One third of all patients attending the Bristol motor neurone (MND) centre elected to use this service.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neuron (MN) disorder, characterized by degeneration of MNs leading to progressive paralysis and death within two to five years after diagnosis. Gene therapy is emerging as promising treatment option for patients affected by familial forms of ALS (fALS), representing 10% of all ALS cases. Taking advantage of viral vectors derived from Adeno-Associated Virus serotype 10 (AAV10) and the small nuclear RNA U7, we developed a gene therapy for SOD1-linked ALS (20% of fALS).
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Authors: Trostchansky A Abstract Amyotrophic lateral sclerosis (ALS) is a multifactorial neurodegenerative disease involving motor neuron (MN) degeneration in the spinal cord, brain stem and primary motor cortex. The existence of inflammatory processes around MN and axonal degeneration in ALS has been shown. Unfortunately, none of the successful therapies in ALS animal models has improved clinical outcomes in patients with ALS. Therefore, the detection of blood biomarkers to be used as screening tools for disease onset and progression has been an expanding research area with few advances in the development of drugs...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Cell Death &Differentiation, Published online: 30 September 2019; doi:10.1038/s41418-019-0422-6LanCL1 promotes motor neuron survival and extends the lifespan of amyotrophic lateral sclerosis mice
Source: Cell Death and Differentiation - Category: Cytology Authors: Source Type: research
Discussion Benign fasciculations are very common and occur in up to 70% of the general population. They occur at different points in people’s lives. They can be brought out by stress, poor sleep hygiene and caffeine. Caffeine has numerous uses especially for regulating sleep and attention. However too much can cause restlessness, jitteriness and sleep deprivation too. The recommended amount of caffeine for a teenager is
Source: - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
AbstractBackgroundRespiratory failure represents an unavoidable step in patients with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND). The development of diaphragm ultrasonography (DUS) provides an alternative useful and risk-free tool to supply clinical, functional, and neurophysiological assessment of respiratory muscle weakness. Our aim was to evaluate if sonographic changes (thickness and echogenicity in the costal portion of the diaphragm, at rest and during respiratory movements) may be used in ALS patients to assess disease severity over time, to rule out any risk or discomfort due to tradi...
Source: Neurological Sciences - Category: Neurology Source Type: research
Authors: Ralli M, Lambiase A, Artico M, de Vincentiis M, Greco A Abstract BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the progressive death of motor neurons leading to fatal paralysis. The causes of ALS remain unknown; however, evidence supports the presence of autoimmune mechanisms contributing to pathogenesis. Although several environmental factors have been proposed, the only established risk factors are older age, male gender, and a family history of ALS. To date, there are no diagnostic test for ALS, and clinicians rely on the combination of upper motor neur...
Source: The Israel Medical Association Journal - Category: General Medicine Tags: Isr Med Assoc J Source Type: research
This article is protected by copyright. All rights reserved. PMID: 31509351 [PubMed - as supplied by publisher]
Source: Anatomical Record - Category: Anatomy Authors: Tags: Anat Rec (Hoboken) Source Type: research
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