- UNC13A in amyotrophic lateral sclerosis: from genetic association to therapeutic target. [Review]J Neurol Neurosurg Psychiatry. 2023 Feb 03 [Online ahead of print]JN
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with limited treatment options and an incompletely understood pathophysiology. Although genomewide association studies (GWAS) have advanced our understanding of the disease, the precise manner in which risk polymorphisms contribute to disease pathogenesis remains unclear. Of relevance, GWAS have shown that a polymorphism (rs…
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- Sigma-1 receptor maintains ATAD3A as a monomer to inhibit mitochondrial fragmentation at the mitochondria-associated membrane in amyotrophic lateral sclerosis. [Journal Article]Neurobiol Dis. 2023 Feb 01 [Online ahead of print]ND
- Organelle contact sites are multifunctional platforms for maintaining cellular homeostasis. Alternations of the mitochondria-associated membranes (MAM), one of the organelle contact sites where the endoplasmic reticulum (ER) is tethered to the mitochondria, have been involved in the pathogenesis of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). However, the detailed me…
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- SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS. [Journal Article]Cell Stem Cell. 2023 Feb 02; 30(2):171-187.e14.CS
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by many diverse genetic etiologies. Although therapeutics that specifically target causal mutations may rescue individual types of ALS, such approaches cannot treat most patients since they have unknown genetic etiology. Thus, there is a critical need for therapeutic strategies that rescue multiple forms of ALS. Here,…
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- Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: outcomes of a dedicated anesthesia and surgery protocol. [Journal Article]Surg Endosc. 2023 Feb 03 [Online ahead of print]SE
- CONCLUSIONS: Protocols for optimizing PEG may help overcome challenges present in the ALS patient population. Despite patient comorbidities, protocol implementation and dedicated team members resulted in a high procedural success rate and low complication rate. Further study is warranted to optimize the timing of PEG placement in relation to ALS disease progression and determine the utility of regional anesthesia during PEG placement.
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- Trends in the diagnostic delay and pathway for amyotrophic lateral sclerosis patients across different countries. [Journal Article]Front Neurol. 2022; 13:1064619.FN
- CONCLUSIONS: We suggest that a specific diagnostic test for ALS-a specific biomarker-will be needed to achieve early diagnosis. Early referral to a neurologist and to electromyography is important for early ALS diagnosis.
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- Evaluating the contribution of the gene TARDBP in Italian patients with amyotrophic lateral sclerosis. [Journal Article]Eur J Neurol. 2023 Feb 02 [Online ahead of print]EJ
- CONCLUSIONS: In our cohort, TARDBP variants have a relevant frequency in Italian ALS patients and they are significantly associated to cognitive impairment. Clinical presentation is heterogeneous. Consistent genotype-phenotype correlations are limited to some mutations. A marked phenotypic variability characterizes the p.A382T variant, suggesting a multifactorial/oligogenic pathogenic mechanism.
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- Leveraging process mining for modeling progression trajectories in amyotrophic lateral sclerosis. [Journal Article]BMC Med Inform Decis Mak. 2023 Feb 02; 22(Suppl 6):346.BM
- CONCLUSIONS: We exploited PM to provide an overview of the evolution scenarios of an ALS trial population and to preliminary compare it to the progression observed in a clinical cohort. Future work will focus on further improving the understanding of the disease progression mechanisms, by including additional real-world subjects as well as by extending the set of events considered in the impairment trajectories.
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- A cellular taxonomy of the adult human spinal cord. [Journal Article]Neuron. 2023 Feb 01; 111(3):328-344.e7.N
- The mammalian spinal cord functions as a community of cell types for sensory processing, autonomic control, and movement. While animal models have advanced our understanding of spinal cellular diversity, characterizing human biology directly is important to uncover specialized features of basic function and human pathology. Here, we present a cellular taxonomy of the adult human spinal cord using…
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- The Serotonergic System and Amyotrophic Lateral Sclerosis: A Review of Current Evidence. [Review]Cell Mol Neurobiol. 2023 Feb 02 [Online ahead of print]CM
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the premature death of motor neurons. Serotonin (5-HT) is a crucial neurotransmitter, and its dysfunction, whether as a contributor or by-product, has been implicated in ALS pathogenesis. Here, we summarize current evidence linking serotonergic alterations to ALS, including results from post-mortem and neuroimagi…
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- Retinal nerve fiber layer thinning found in amyotrophic lateral sclerosis - Correlation with disease duration and severity. [Journal Article]Indian J Ophthalmol. 2023 Feb; 71(2):369-378.IJ
- CONCLUSIONS: The retinal changes can serve as a marker for diagnosing and monitoring patients with ALS.
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- Microemboli induced by air bubbles may be deposited in organs as a consequence of contamination during medical care. [Journal Article]
- CONCLUSIONS: More ME were present in HD patients compared with those who suffered from ALS. Minimizing air contamination from syringes, infusions and bloodlines will decrease ME and subsequent tissue injury.
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- Involvement of heterologous ubiquitination including linear ubiquitination in Alzheimer's disease and amyotrophic lateral sclerosis. [Review]
- In neurodegenerative diseases such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), the progressive accumulation of ubiquitin-positive cytoplasmic inclusions leads to proteinopathy and neurodegeneration. Along with the seven types of Lys-linked ubiquitin chains, the linear ubiquitin chain assembly complex (LUBAC)-mediated Met1-linked linear ubiquitin chain, which activates the…
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- Restoring arm function with a soft robotic wearable for individuals with amyotrophic lateral sclerosis. [Journal Article]Sci Transl Med. 2023 Feb; 15(681):eadd1504.ST
- Despite promising results in the rehabilitation field, it remains unclear whether upper limb robotic wearables, e.g., for people with physical impairments resulting from neurodegenerative disease, can be made portable and suitable for everyday use. We present a lightweight, fully portable, textile-based, soft inflatable wearable robot for shoulder elevation assistance that provides dynamic active…
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- Dysregulation of Gene Expressions in Multiple Sclerosis: TNFSF13B and Other Candidate Genes. [Journal Article]J Integr Neurosci. 2022 Nov 25; 22(1):4.JI
- CONCLUSIONS: Although with caution due to the small sample size, this study confirms the interest in transcriptomic analysis supported by integrated and educated bioinformatics evaluations, to shed further light in complex neurological diseases.
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- SBT-272 improves TDP-43 pathology in ALS upper motor neurons by modulating mitochondrial integrity, motility, and function. [Journal Article]Neurobiol Dis. 2023 Jan 27; 178:106022.ND
- Mitochondrial defects are one of the common underlying causes of neuronal vulnerability in neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), and TDP-43 pathology is the most commonly observed proteinopathy. Disrupted inner mitochondrial membrane (IMM) reported in the upper motor neurons (UMNs) of ALS patients with TDP-43 pathology is recapitulated in the UMNs of well-charac…
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- The cutaneous silent period as a measure of upper motor neuron dysfunction in amyotrophic lateral sclerosis. [Journal Article]Neurophysiol Clin. 2023 Jan 28; 53(4):102843.NC
- CONCLUSIONS: We conclude that upper limb CutSP changes associates with UMN lesion in ALS. This neurophysiological measurement merits further investigation in ALS.
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- Exploring the Folding Mechanism of Dimeric Superoxide Dismutase. [Journal Article]J Phys Chem B. 2023 Jan 30 [Online ahead of print]JP
- The Cu/Zn Human Superoxide Dismutase (SOD1) is a dimeric metalloenzyme whose genetic mutations are directly related to amyotrophic lateral sclerosis (ALS), so understanding its folding mechanism is of fundamental importance. Currently, the SOD1 dimer formation is studied via molecular dynamics simulations using a simplified structure-based model and an all-atom model. Results from the simplified …
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- An Exploratory Trial of EPI-589 in Amyotrophic Lateral Sclerosis (EPIC-ALS): Protocol for a Multicenter, Open-Labeled, 24-Week, Single-Group Study. [Journal Article]JMIR Res Protoc. 2023 Jan 30; 12:e42032.JR
- CONCLUSIONS: This study can provide useful data to understand the characteristics of EPI-589.
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- Incidence of Syndromes Associated With Frontotemporal Lobar Degeneration in 9 European Countries. [Journal Article]JAMA Neurol. 2023 Jan 30 [Online ahead of print]JN
- CONCLUSIONS: The findings suggest that FTLD-associated syndromes are more common than previously recognized, and diagnosis should be considered at any age. Improved knowledge of FTLD incidence may contribute to appropriate health and social care planning and in the design of future clinical trials.
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- Clinical relevance of macroglossia to disease progression in ventilation dependent patients with advanced ALS. [Journal Article]Neurol Sci. 2023 Jan 30 [Online ahead of print]NS
- CONCLUSIONS: Macroglossia in advanced ALS with invasive ventilation is associated with disease progression.
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- Nutraceuticals and phytotherapeutics for holistic management of amyotrophic lateral sclerosis. [Review]
- Amyotrophic lateral sclerosis" (ALS) is a progressive neuronal disorder that affects sensory neurons in the brain and spinal cord, causing loss of muscle control. Moreover, additional neuronal subgroups as well as glial cells such as microglia, astrocytes, and oligodendrocytes are also thought to play a role in the aetiology. The disease affects upper motor neurons and lowers motor neurons and le…
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- Complementary Medicine and Expressive Arts Therapy: Adjuvant for Recovery Following Neurosurgical Procedures. [Journal Article]
- Art as a way of healing is primordial in many cultures. Expressive Arts Therapy (ExAT) uses art, music, dance, and writing to help individuals navigate their healing journey. Patient self-expression as a mode of recovery has been observed in patients with Parkinson's disease, epilepsy, Amyotrophic Lateral Sclerosis (ALS) and cancer. Complementary medical approaches such as acupuncture and mindful…
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- Filtered Cerebrospinal Fluid From Patients With Amyotrophic Lateral Sclerosis Displays an Altered Proteome and Affects Motor Phenotype in a Mouse Model. [Journal Article]
- CONCLUSIONS: We demonstrated the ability to filter proteins from the CSF of ALS patients and identified potentially pathologic proteins that were reduced in quantity. Additionally, we demonstrated the ability of unfiltered ALS-CSF to induce motor deficits in mice on the pole descent and open field tests and showed that filtration could prevent this deficit. Given the lack of effective treatments for ALS, this could be a novel solution for patients suffering from this deadly and irreversible condition.
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- Single nucleus multiome analysis of the prefrontal cortex from C9orf72 ALS/FTD patients illuminates pathways affected during disease progression. [Preprint]bioRxiv. 2023 Jan 13B
- Repeat expansions in the C9orf72 gene are the most common genetic cause of amyotrophic lateral sclerosis and familial frontotemporal dementia (ALS/FTD). To identify molecular defects that take place in the dorsolateral frontal cortex of patients with C9orf72 ALS/FTD, we compared healthy controls with C9orf72 ALS/FTD donor samples staged based on the levels of cortical phosphorylated TAR DNA bindi…
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- A high-performance speech neuroprosthesis. [Preprint]bioRxiv. 2023 Jan 21B
- Speech brain-computer interfaces (BCIs) have the potential to restore rapid communication to people with paralysis by decoding neural activity evoked by attempted speaking movements into text 1,2 or sound 3,4 .Early demonstrations, while promising, have not yet achieved accuracies high enough for communication of unconstrainted sentences from a large vocabulary 1â€"5 . Here, we demonstrate the fi…
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- A dual MTOR/NAD+ acting gerotherapy. [Preprint]bioRxiv. 2023 Jan 19B
- The geroscience hypothesis states that a therapy that prevents the underlying aging process should prevent multiple aging related diseases. The mTOR (mechanistic target of rapamycin)/insulin and NAD+ (nicotinamide adenine dinucleotide) pathways are two of the most validated aging pathways. Yet, it’s largely unclear how they might talk to each other in aging. In genome-wide CRISPRa screening wit…
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- Three nervous system-specific expressed genes are potential biomarkers for the diagnosis of sporadic amyotrophic lateral sclerosis through a bioinformatic analysis. [Journal Article]
- CONCLUSIONS: Our results identified three nervous system-specific expressed hub genes that might be diagnostic and prognostic markers of sALS and APP might be a genetic susceptibility factor contributing to sALS development.
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- Mechanistic insights into the conformational switch in profilin-1 subject to collective effects of mutation and histidine tautomerism. [Journal Article]Int J Biol Macromol. 2023 Jan 24; 230:123403.IJ
- Mutations and histidine (His) tautomerism in profilin-1 (PFN1) are associated with amyotrophic lateral sclerosis (ALS). The conformational changes in PFN1 caused by the collective effects of G117V mutation and His tautomeric isomers εε, εδ, δε, and δδ were clarified using molecular dynamics (MD) simulations. The predominant structural variations were seen in α-helices, β-sheets, turns, and coils …
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- An evaluation of the combination of sodium phenylbutyrate and taurursodiol for the treatment of amyotrophic lateral sclerosis. [Journal Article]Expert Rev Neurother. 2023 Feb 01 [Online ahead of print]ER
- Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative motor neuron disease. Despite the overwhelming need for effective therapeutics for ALS, riluzole and edaravone were the only two FDA-approved disease-modifying therapies prior to 2022. The randomized, double-blind, multicenter, placebo-controlled CENTAUR trial demonstrated the safety and efficacy of sodium pheny…
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- Blood-CNS barrier dysfunction in amyotrophic lateral sclerosis: Proposed mechanisms and clinical implications. [Review]J Cereb Blood Flow Metab. 2023 Jan 26 [Online ahead of print]JC
- There is strong evidence for blood-brain and blood-spinal cord barrier dysfunction at the early stages of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Since impairment of the blood-central nervous system barrier (BCNSB) occurs during the pre-symptomatic stages of ALS, the mechanisms underlying this pathology are likely also involved in the ALS disease process. I…
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