Expression of Human Endogenous Retrovirus-K in Spinal and Bulbar Muscular Atrophy

Conclusions: Our findings indicate that ERVK expression and activity in SBMA is an unrecognized biomarker and facet of the disease. We discuss how our current understanding of ERVK-driven pathology may tie into key aspects of multi-system dysfunction in SBMA, with a focus on inflammation, proteinopathy, as well as DNA damage and repair.
Source: Frontiers in Neurology - Category: Neurology Source Type: research

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Conclusion and Perspectives The IL-6/JAK/STAT signaling cascade plays a dominant role in skeletal muscle pathophysiology. IL-6 autocrine, paracrine, and endocrine functions assign to its downstream effectors pivotal importance in skeletal muscle-wasting-associated diseases and other multiple system diseases where muscle acts in communication with other organs. Targeting the components of the JAK/STAT pathway recently emerged as a strategic approach for the treatment of inflammatory diseases and human cancer. This review highlights the opposite outcomes on muscle biology caused by the amount of local and systemic release ...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Genome damage and their defective repair have been etiologically linked to degenerating neurons in many subtypes of amyotrophic lateral sclerosis (ALS) patients; however, the specific mechanisms remain enigmatic. The majority of sporadic ALS patients feature abnormalities in the transactivation response DNA-binding protein of 43 kDa (TDP-43), whose nucleo-cytoplasmic mislocalization is...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
An extensive microglial-astrocyte-monocyte-neuronal cross talk seems to be crucial for normal brain function, development, and recovery. However, under certain conditions neuroinflammatory interactions between brain cells and neuroimmune cells influence disease outcome and brain pathology. Microglial cells express a range of functional states with dynamically pleomorphic profiles from a surveilling status of synaptic transmission to an active player in major events of development such as synaptic elimination, regeneration, and repair. Also, inflammation mediates a series of neurotoxic roles in neuropsychiatric conditions a...
Source: Neuroimmunomodulation - Category: Allergy & Immunology Source Type: research
Frontotemporal dementia (FTD), the second most common form of dementia in people under 65 years of age, is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD overlaps extensively with the motor neuron disease amyotrophic lateral sclerosis (ALS), especially at the genetic level. Both FTD and ALS can be caused by many mutations in the same set of genes; the most prevalent of these mutations is a GGGGCC repeat expansion in the first intron of C9ORF72. As shown by recent intensive studies, some key cellular pathways are dysregulated in the ALS-FTD spectrum disorder, including autophagy, nucleoc...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Molecular Biology of Disease, Neuroscience Review Source Type: research
Conclusions:The involvement we observed in miRNAs is related to muscle atrophy and repair of neuromuscular junction, in addition we observed an increase in male gender of microRNAs expression and dysregulation of inflammatory microRNAs.Disclosure: Dr. Pegoraro has nothing to disclose. Dr. Angelini has received personal compensation for activities with Sanofi Genzyme as an advisory board member.
Source: Neurology - Category: Neurology Authors: Tags: Neuromuscular and Clinical Neurophysiology (EMG): Motor Neuron Disease II Source Type: research
Conclusions:This case demonstrates that anterior spinal cyst may manifest as atypical motor neuron disease, such as Hirayama or amyotrophic lateral sclerosis. Also, it enforces the importance of obtaining radiographic images to asses in evaluating the spine when electromyography and physical exam is inconclusive. To our knowledge, "Snake Eyes" sign has not been reported in anterior epidural spinal cyst. In addition, including anterior cervical spinal cyst in the differential diagnosis of progressive upper extremity weakness and atrophy is important, as this may lead to definitive, attenuating, and possibly curati...
Source: Neurology - Category: Neurology Authors: Tags: Neuromuscular and Clinical Neurophysiology (EMG): Motor Neuron Disease II Source Type: research
The developmental morphogen Sonic hedgehog (Shh) may continue to play a sustaining role in adult motor neurons, of potential relevance to motor neuron diseases including amyotrophic lateral sclerosis. The Shh signaling pathway is incompletely understood and interactions with other signaling pathways are possible. We focus here on Notch, and first show that there is an almost linear reduction in light output from a Gli reporter in Shh Light II cells in the presence of increasing concentrations of the Notch inhibitor DAPT (r2=0.982). Second, in the spinal cord of mutant superoxide dismutase mice, but not control mice, a key ...
Source: NeuroReport - Category: Neurology Tags: Degeneration and Repair Source Type: research
Publication date: Available online 15 January 2017 Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms Author(s): Ravindra N. Singh, Matthew D. Howell, Eric W. Ottesen, Natalia N. Singh The multifunctional Survival Motor Neuron (SMN) protein is required for the survival of all organisms of the animal kingdom. SMN impacts various aspects of RNA metabolism through the formation and/or interaction with ribonucleoprotein (RNP) complexes. SMN regulates biogenesis of small nuclear RNPs, small nucleolar RNPs, small Cajal body-associated RNPs, signal recognition particles and telomerase. SMN also plays an impo...
Source: Biochimica et Biophysica Acta (BBA) Gene Regulatory Mechanisms - Category: Genetics & Stem Cells Source Type: research
Abstract The multifunctional Survival Motor Neuron (SMN) protein is required for the survival of all organisms of the animal kingdom. SMN impacts various aspects of RNA metabolism through the formation and/or interaction with ribonucleoprotein (RNP) complexes. SMN regulates biogenesis of small nuclear RNPs, small nucleolar RNPs, small Cajal body-associated RNPs, signal recognition particles and telomerase. SMN also plays an important role in DNA repair, transcription, pre-mRNA splicing, histone mRNA processing, translation, selenoprotein synthesis, macromolecular trafficking, stress granule formation, cell signali...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research
Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron dysfunction disease that leads to paralysis and death. There is currently no established molecular pathogenesis pathway. Multiple proteins involved in RNA processing are linked to ALS, including FUS and TDP43, and we propose a disease mechanism in which loss of function...
Source: Proceedings of the National Academy of Sciences - Category: Science Authors: Tags: PNAS Plus Source Type: research
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