Amyotrophic Lateral Sclerosis: Autoimmune Pathogenic Mechanisms, Clinical Features, and Therapeutic Perspectives.

Amyotrophic Lateral Sclerosis: Autoimmune Pathogenic Mechanisms, Clinical Features, and Therapeutic Perspectives. Isr Med Assoc J. 2019 Jul;21(7):438-443 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 neuron and lower motor neuron signs in the same body region. The aim of this paper was to provide a comprehensive review of current clinical literature with special focus on the role of autoimmunity in ALS, differential diagnosis, and available therapeutic approaches. Current evidence suggests a contribution of the innate immune system in ALS, with a role of microglial cell activation at the sites of neurodegeneration. The median time from symptom onset to diagnosis of ALS is 14 months, and this time estimate is mainly based on specific clinical signs and exclusion of ALS-like conditions. Several therapeutic approaches have been proposed, including immunosuppressive drugs, to reduce disease progres...
Source: The Israel Medical Association Journal - Category: General Medicine Tags: Isr Med Assoc J Source Type: research

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Conclusion and Perspectives The ARE has been studied for a long time, and about 20 ARE-BPs have been identified since discovery of first ARE-BP, AUF1 (Brewer, 1991; Garcia-Maurino et al., 2017). The specific target mRNAs for different ARE-BPs, as well as their molecular functions on these mRNAs, and contribution of this regulation to specific biological processes are gradually being uncovered. However, with a few exceptions, the molecular mechanisms used by ARE-BPs to regulate their targets are still unknown. In particular, the mechanism to recognize and control specific targets from the large number of transcripts t...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
AbstractAquaporin 4 (AQP4) is a primary water channel found on astrocytes in the central nervous system (CNS). Besides its function in water and ion homeostasis, AQP4 has also been documented to be involved in a myriad of acute and chronic cerebral pathologies, including autoimmune neurodegenerative diseases. AQP4 has been postulated to be associated with the incidence of a progressive neurodegenerative disorder known as amyotrophic lateral sclerosis (ALS), a disease that targets the motor neurons, causing muscle weakness and eventually paralysis. Raised AQP4 levels were noted in association with vessels surrounded with sw...
Source: Neurological Sciences - Category: Neurology Source Type: research
Conclusions: We demonstrated in the SOD1G93A model of ALS that increased levels of several cytokines were associated with a shorter lifespan. However, their role as prognostic biomarkers is unclear as their expression was very variable depending on both the disease stage and the subject. Nevertheless, cytokines may be potential therapeutic targets. Introduction Amyotrophic Lateral Sclerosis (ALS) is one of the most common rare diseases of unknown origin that leads to progressive motor neuron degeneration and muscle denervation (1). In particular, it has been described that either distal axonopathy or neuromuscular ju...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions The momentous advances in spinal imaging in ALS suggest the spinal metrics may soon be used as validated diagnostic, monitoring, and prognostic markers, contributing both to individualized patient care and pharmacological trials. Author Contributions ME, GQ, PB, and P-FP contributed equally to the conceptualization, drafting, and revision of the manuscript. Funding Peter Bede is supported by the Health Research Board (HRB—Ireland; HRB EIA-2017-019), the Iris O'Brien Foundation, the Irish Institute of Clinical Neuroscience IICN—Novartis Ireland Research Grant, and the Research Motor Neur...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
Authors: Arbizu J, Giuliani A, Perez-Larraya JG, Riverol M, Jonsson C, García-García B, Morales M, Imaz L, Pagani M Abstract PET using 18F-2-fluoro-2-deoxy-D-glucose (FDG-PET) has been gradually introduced in the diagnostic clinical criteria of the most prevalent neurodegenerative diseases. Moreover, an increasing amount of literature have shown that the information provided by FDG-PET enhances the sensitivity of standard imaging biomarkers in less frequent disorders in which an early differential diagnosis can be of paramount relevance for patient management and outcome. Therefore emerging uses of FD...
Source: Quarterly Journal of Nuclear Medicine and Molecular Imaging - Category: Nuclear Medicine Tags: Q J Nucl Med Mol Imaging Source Type: research
ahy N Abstract Research into the pathogenesis of amyotrophic lateral sclerosis (ALS) has obtained notable gene discoveries, although, to date, only progress with regard to treatment has been very modest. Currently ALS is considered a multifactorial disease that presents diverse clinical presentations, ranging from a monogenic inherited disease to an autoimmune pathology, and develops with misfolded protein aggregation and neuroinflammation. An important factor related to ALS pathogenesis is the microglial activation associated with degenerative motor neurons. This activation leads to changes in the expression of a...
Source: Current Medicinal Chemistry - Category: Chemistry Authors: Tags: Curr Med Chem Source Type: research
Conclusions: The association between selective autoimmune disease and neurodegenerative disorders unified by the underlying pathology frontotemporal lobar degeneration with TDP-43–positive inclusions (FTLD-TDP) extends to C9 and FTD/MND cohorts, providing further evidence that select autoimmune inflammation may be intrinsically linked to FTLD-TDP pathophysiology.
Source: Neurology Neuroimmunology and Neuroinflammation - Category: Neurology Authors: Tags: Autoimmune diseases, Amyotrophic lateral sclerosis, Frontotemporal dementia, Case control studies Article Source Type: research
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. Although the etiology of ALS is obscure, genetic studies of familiar ALS suggest a multifactorial etiology for this condition. Similarly, there probably are multiple causes for sporadic ALS. Autoimmune-mediated motor neuron dysfunction is one proposed etiology for sporadic ALS. In the present study, anti-glycolipid antibodies including GM1, GD1b, GD3, and sulfoglucuronosyl paragloboside (SGPG) were investigated in the sera of a large number of patient samples, including 113 ALS pati...
Source: ASN Neuro - Category: Neuroscience Authors: Tags: Original Article Source Type: research
When evaluating a patient with progressive weakness for the first time, it is occasionally difficult to distinguish a motor neuron disease from an autoimmune neuromuscular disorder. Our neurological testing may even cloud the picture, as nearly 1/3 of patients with amyotrophic lateral sclerosis (ALS) may have decrement on repetitive nerve stimulation [1] and the risk of ALS is increased in people with concomitant autoimmune disease including myasthenia gravis (MG) [2]. In this context, the neurologist may wish to commence immunotherapy given the dismal alternative.
Source: Neuromuscular Disorders - Category: Neurology Authors: Tags: Editorial Source Type: research
Conclusions: These data indicate that an ALS syndrome might be related to autoimmunity and gluten sensitivity. As gluten sensitivity is potentially treatable, this diagnostic challenge should not be overlooked.Disclosure: Dr. Drory has nothing to disclose. Dr. Gadoth has nothing to disclose. Dr. Bleiberg has nothing to disclose. Dr. Klein has nothing to disclose. Dr. Nefussy has nothing to disclose.
Source: Neurology - Category: Neurology Authors: Tags: Neuroepidemiology: Movement Disorders, ALS, and Neuromuscular Source Type: research
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