Structural Properties and Interaction Partners of Familial ALS-Associated SOD1 Mutants

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron degenerative disease in adults and has also been proven to be a type of conformational disease associated with protein misfolding and dysfunction. To date, more than 150 distinct genes have been found to be associated with ALS, among which Superoxide Dismutase 1 (SOD1) is the first and the most extensively studied gene. It has been well established that SOD1 mutants-mediated toxicity is caused by a gain-of-function rather than the loss of the detoxifying activity of SOD1. Compared with the clear autosomal dominant inheritance of SOD1 mutants in ALS, the potential toxic mechanisms of SOD1 mutants in motor neurons remain incompletely understood. A large body of evidence has shown that SOD1 mutants may adopt a complex profile of conformations and interact with a wide range of client proteins. Here, in this review, we summarize the fundamental conformational properties and the gained interaction partners of the soluble forms of the SOD1 mutants which have been published in the past decades. Our goal is to find clues to the possible internal links between structural and functional anomalies of SOD1 mutants, as well as the relationships between their exposed epitopes and interaction partners, in order to help reveal and determine potential diagnostic and therapeutic targets
Source: Frontiers in Neurology - Category: Neurology Source Type: research

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Source: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration - Category: Neurology Authors: Source Type: research
Abstract Routine quantitative electromyography is used for the assessment of the presence of lower motor neurone involvement and its consequences, including primary denervation and compensatory reinnervation of muscle fibres. However, it is not useful for the assessment of the motor unit number reserve. The need for a valid biomarker to evaluate lower motor neurone disease progression in such diseases as amyotrophic lateral sclerosis, and for use in clinical trials, has led to a number of studies of the methods that allow assessment of the number of motor units. In this review, motor unit number estimation (MUNE) ...
Source: Neurologia i Neurochirurgia Polska - Category: Neurology Authors: Tags: Neurol Neurochir Pol Source Type: research
Authors: Yamaura G, Higashiyama Y, Kusama K, Kunii M, Tanaka K, Koyano S, Nakashima M, Tsurusaki Y, Miyake N, Saitsu H, Iwahashi Y, Joki H, Matsumoto N, Doi H, Tanaka F Abstract A 24-year-old Japanese man exhibited slowly progressive gait disturbance from childhood to young adulthood. Physical and physiological examinations showed the involvement of both upper and lower motor neurons, fulfilling the diagnostic criteria for amyotrophic lateral sclerosis (ALS). Mild cognitive impairment and subclinical sensory involvement were also observed. A genetic analysis revealed novel compound heterozygous mutations, c.767C>...
Source: Internal Medicine - Category: Internal Medicine Tags: Intern Med Source Type: research
Abstract We used transcranial magnetic stimulation (TMS) of motor cortex, including a novel four-pulse superconditioning (TMSsc) paradigm, in repeated examinations of motor-evoked potentials (MEPs) in eight subjects with motor neuron disease (MND), including seven with amyotrophic lateral sclerosis (ALS). The goals were: (1) to look for evidence of cortical hyperexcitability, including a reduction in short-interval intracortical inhibition (SICI); and (2) to examine the utility of using TMSsc for quantifying upper motor neuron function during MND progression. Testing of abductor pollicis brevis (APB) and tibialis ...
Source: Experimental Brain Research - Category: Neuroscience Authors: Tags: Exp Brain Res Source Type: research
β-catenin aggregation in models of ALS motor neurons: GSK3β inhibition effect and neuronal differentiation. Neurobiol Dis. 2019 Jun 06;:104497 Authors: Pinto C, Medinas DB, Fuentes-Villalobos F, Maripillán J, Castro AF, Martínez AD, Osses N, Hetz C, Henríquez JP Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by motor neuron death. A 20% of familial ALS cases are associated with mutations in the gene coding for superoxide dismutase 1 (SOD1). The accumulation of abnormal aggregates of different proteins is a common feature in moto...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research
In this study, using primary mixed glial cultures from different mouse CNS regions (spinal cord and cortex), we examined whether regional differences exist in key glial pathways that contribute to, or protect against, motor neuron degeneration. Specifically, we examined the NF-κB-mediated inflammatory pathway and the cytoprotective heat shock response (HSR). Glial cultures were treated with pro-inflammatory stimuli, tumour necrosis factor-ɑ/lipopolysaccharide or heat stressed to stimulate the inflammatory and HSR respectively. We found that spinal cord glia expressed more iNOS and produced more NO compared to cortic...
Source: Cell Stress and Chaperones - Category: Cytology Authors: Tags: Cell Stress Chaperones Source Type: research
PMID: 31171431 [PubMed - as supplied by publisher]
Source: Clinical Neurophysiology - Category: Neurology Authors: Tags: Clin Neurophysiol Source Type: research
Conclusion: Overall, and even though we must account for the limitations of the indirect methods and models used for prevalence estimation, we probably have a very high ALS/MND prevalence in Portugal. It would be important to create registries, particularly in rare diseases, for better organization and distribution of healthcare services and resources, particularly at the level of ventilatory support.Neuroepidemiology
Source: Neuroepidemiology - Category: Epidemiology Source Type: research
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Source: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration - Category: Neurology Authors: Source Type: research
Mir-17∼92 Confers Motor Neuron Subtype Differential Resistance to ALS-Associated Degeneration. Cell Stem Cell. 2019 May 21;: Authors: Tung YT, Peng KC, Chen YC, Yen YP, Chang M, Thams S, Chen JA Abstract Progressive degeneration of motor neurons (MNs) is the hallmark of amyotrophic lateral sclerosis (ALS). Limb-innervating lateral motor column MNs (LMC-MNs) seem to be particularly vulnerable and are among the first MNs affected in ALS. Here, we report association of this differential susceptibility with reduced expression of the mir-17∼92 cluster in LMC-MNs prior to disease onset. Reduced mir-...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
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