Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders.

Modulating the Folding Landscape of Superoxide Dismutase 1 with Targeted Molecular Binders. Angew Chem Int Ed Engl. 2018 Apr 12;: Authors: Bunck DN, Atsavapranee B, Museth AK, VanderVelde D, Heath JR Abstract Amyotrophic lateral sclerosis, or Lou Gehrig's disease, is characterized by motor neuron death with average survival times of 2 - 5 years. One cause of this disease is the misfolding of superoxide dismutase 1 (SOD1), a protein whose stability and aggregation propensity are affected by point mutations spanning the protein. Here, we use an epitope-specific, high-throughput screen to identify peptides that both stabilize the native conformation of SOD1 as well as accelerate its folding by 2.5-fold. Ligands targeted to the electrostatic loop on the periphery of the protein tightened the non-metalated structure and accelerated its folding. This strategy may be useful for fundamental studies of protein energy landscapes as well as designing new classes of therapeutics. PMID: 29645329 [PubMed - as supplied by publisher]
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research

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Our objective was to quantify health service utilisation including monitoring and treatment of respiratory complications for adults with neuromuscular disease (NMD), identifying practice variation and adherence to guideline recommendations at a population level. We conducted a population-based longitudinal cohort study (2003–2015) of adults with NMD using hospital diagnostic and health insurance billing codes within administrative health databases. We identified 185 586 adults with NMD. Mean age 52 years, 59% female. 41 173 (22%) went to an emergency department for respiratory complications on average 1.6 times ...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Respiratory clinical practice Original Articles: Neuromuscular disease Source Type: research
Exp Clin Endocrinol Diabetes DOI: 10.1055/a-0672-1007Sarcopenia in geriatric patients is often associated with or even caused by changes of the endocrine and nervous system. The multifactorial pathogenesis of sarcopenia and additional multimorbidity in geriatric patients makes it difficult to study distinct pathogenic pathways leading to sarcopenia. Patients suffering from diabetes, Cushing’s syndrome, chronic kidney disease, Klinefelter’s syndrome or motor neuron diseases, such as amyotrophic lateral sclerosis for example are known to have impaired muscle property and reduced physical performance. These patien...
Source: Experimental and Clinical Endocrinology and Diabetes - Category: Endocrinology Authors: Tags: Review Source Type: research
Publication date: Available online 1 September 2018Source: NeuroscienceAuthor(s): Lori A. Lind, Erika R. Murphy, Teresa E. Lever, Nicole L. NicholsAbstractAmyotrophic lateral sclerosis (ALS) is a devastating disease leading to degeneration of motor neurons and skeletal muscles, including those required for swallowing. Tongue weakness is one of the earliest signs of bulbar dysfunction in ALS, which is attributed to degeneration of motor neurons in the hypoglossal nucleus in the brainstem, the axons of which directly innervate the tongue. Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to...
Source: Neuroscience - Category: Neuroscience Source Type: research
AbstractCerebrospinal fluid (CSF) neurofilament light chain (NfL) has emerged as putative diagnostic biomarker in amyotrophic lateral sclerosis (ALS), but it remains a matter of debate, whether CSF total tau (ttau), tau phosphorylated at threonine 181 (ptau) and the ptau/ttau ratio could serve as diagnostic biomarker in ALS as well. Moreover, the relationship between CSF NfL and tau measures to further axonal and (neuro)degeneration markers still needs to be elucidated. Our analysis included 89 ALS patients [median (range) age 63 (33 –83) years, 61% male, disease duration 10 (0.2–190) months] and 33 age- and se...
Source: Journal of Neurology - Category: Neurology Source Type: research
Nishita Singh, Sucharita Ray, Achal SrivastavaAnnals of Indian Academy of Neurology 2018 21(3):173-178 Giving a diagnosis of amyotrophic lateral sclerosis to a patient is akin to handing out a death certificate. However, not all patients presenting with the classical dysphagia, wasting, and weakness may have motor neuron diseases. In these cases, it is extremely important not to miss little cues which can suggest an alternative diagnosis and in many cases a lease of life in terms of a treatment option. In this review, we consider some clinical scenarios that can present with the same symptom complex as diseases involving ...
Source: Annals of Indian Academy of Neurology - Category: Neurology Authors: Source Type: research
Publication date: Available online 1 September 2018Source: NeuroscienceAuthor(s): Lori A. Lind, Erika R. Murphy, Teresa E. Lever, Nicole L. NicholsAbstractAmyotrophic lateral sclerosis (ALS) is a devastating disease leading to degeneration of motor neurons and skeletal muscles, including those required for swallowing. Tongue weakness is one of the earliest signs of bulbar dysfunction in ALS, which is attributed to degeneration of motor neurons in the hypoglossal nucleus in the brainstem, the axons of which directly innervate the tongue. Despite its fundamental importance, dysphagia (difficulty swallowing) and strategies to...
Source: Neuroscience - Category: Neuroscience Source Type: research
This article is protected by copyright. All rights reserved. PMID: 30175403 [PubMed - as supplied by publisher]
Source: The Journal of Physiology - Category: Physiology Authors: Tags: J Physiol Source Type: research
Purpose of review Neuroinflammation is increasingly recognized as an important mediator of disease progression in patients with amyotrophic lateral sclerosis (ALS), and is characterized by reactive central nervous system (CNS) microglia and astroglia as well as infiltrating peripheral monocytes and lymphocytes. Anti-inflammatory and neuroprotective factors sustain the early phase of the disease whereas inflammation becomes proinflammatory and neurotoxic as disease progression accelerates. Initially, motor neurons sustain injuries through multiple mechanisms resulting from harmful mutations causing disruptions of critical...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Jeremy Shefner and Shafeeq S. Ladha Source Type: research
Purpose of review Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of the motor neurons, characterized by upper motor neuron (UMN) and lower motor neuron (LMN) dysfunction. There have been significant technological advances in the development of neurophysiological biomarkers of UMN and LMN dysfunction in ALS. In this review, we discuss major advances in development of neurophysiological biomarkers in ALS, critiquing their potential in diagnosis and prognosis of ALS, as well as utility in monitoring treatment effects. Recent findings The threshold tracking transcranial magnetic st...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Jeremy Shefner and Shafeeq S. Ladha Source Type: research
Purpose of review Amyotrophic lateral sclerosis (ALS) is a rapidly fatal disease for which there is currently no effective therapy. The present review describes the current progress of existing molecular therapies in the clinical trial pipeline and highlights promising future antisense oligonucleotide (ASO) and viral therapeutic strategies for treating ALS. Recent findings The immense progress in the design of clinical trials and generation of ASO therapies directed towards superoxide dismutase-1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) repeat expansion related disease have been propelled by fundamental...
Source: Current Opinion in Neurology - Category: Neurology Tags: MOTOR NEURON DISEASE: Edited by Jeremy Shefner and Shafeeq S. Ladha Source Type: research
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