scholarly journals Therapeutic Depletion of Axotomy Competent Cells in Amyotrophic Lateral Sclerosis (ALS)

2019 ◽  
Vol 2 (1) ◽  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Protein Networks ◽  
Large Protein ◽  
Anatomical Structures ◽  
Therapy Options ◽  
New Therapy ◽  
Competent Cells ◽  
Health And Disease ◽  
Insight Into ◽  
Lateral Sclerosis

The present paper addresses anatomically resolved protein networks by using the Imaging Cycler Microscopy (ICM/TIS) [1,2]. ICM is capable of resolving protein networks in intact anatomical structures at a power of combinatorial molecular resolution of 65,553k , where k is the number of co-mapped proteins, e.g. 100 proteins [1-4]. This method provides insight into the laws of the spatial communication of large protein networks in health and disease, which is essential for new therapy options in diseases.

New therapy options for amyotrophic lateral sclerosis

2013 ◽  
Vol 14 (14) ◽  
pp. 1907-1917 ◽  
Author(s):  
Paul Gordon ◽  
Philippe Corcia ◽  
Vincent Meininger
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Therapy Options ◽  
New Therapy ◽  
Lateral Sclerosis

scholarly journals A modular tool to query and inducibly disrupt biomolecular condensates

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carmen N. Hernández-Candia ◽  
Sarah Pearce ◽  
Chandra L. Tucker
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cellular Function ◽  
Biological Role ◽  
Cellular Biology ◽  
Condensate Formation ◽  
Health And Disease ◽  
Lateral Sclerosis

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.

scholarly journals The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sarah L. Boddy ◽  
Ilaria Giovannelli ◽  
Matilde Sassani ◽  
Johnathan Cooper-Knock ◽  
Michael P. Snyder ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Phenotypic Variability ◽  
Personalised Medicine ◽  
Main Body ◽  
Body Of Knowledge ◽  
Environmental Component ◽  
Health And Disease ◽  
Lateral Sclerosis

Abstract Background Much progress has been made in mapping genetic abnormalities linked to amyotrophic lateral sclerosis (ALS), but the majority of cases still present with no known underlying cause. Furthermore, even in families with a shared genetic abnormality there is significant phenotypic variability, suggesting that non-genetic elements may modify pathogenesis. Identification of such disease-modifiers is important as they might represent new therapeutic targets. A growing body of research has begun to shed light on the role played by the gut microbiome in health and disease with a number of studies linking abnormalities to ALS. Main body The microbiome refers to the genes belonging to the myriad different microorganisms that live within and upon us, collectively known as the microbiota. Most of these microbes are found in the intestines, where they play important roles in digestion and the generation of key metabolites including neurotransmitters. The gut microbiota is an important aspect of the environment in which our bodies operate and inter-individual differences may be key to explaining the different disease outcomes seen in ALS. Work has begun to investigate animal models of the disease, and the gut microbiomes of people living with ALS, revealing changes in the microbial communities of these groups. The current body of knowledge will be summarised in this review. Advances in microbiome sequencing methods will be highlighted, as their improved resolution now enables researchers to further explore differences at a functional level. Proposed mechanisms connecting the gut microbiome to neurodegeneration will also be considered, including direct effects via metabolites released into the host circulation and indirect effects on bioavailability of nutrients and even medications. Conclusion Profiling of the gut microbiome has the potential to add an environmental component to rapidly advancing studies of ALS genetics and move research a step further towards personalised medicine for this disease. Moreover, should compelling evidence of upstream neurotoxicity or neuroprotection initiated by gut microbiota emerge, modification of the microbiome will represent a potential new avenue for disease modifying therapies. For an intractable condition with few current therapeutic options, further research into the ALS microbiome is of crucial importance.

Author response for "Combination of acamprosate and baclofen (PXT864) as a potential new therapy for amyotrophic lateral sclerosis"

2020 ◽  
Author(s):  
Lydie Boussicault ◽  
Julien Laffaire ◽  
Peter Schmitt ◽  
Philippe Rinaudo ◽  
Noëlle Callizot ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Author Response ◽  
New Therapy ◽  
Lateral Sclerosis

scholarly journals d-amino Acids in Health and Disease: A Focus on Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2205 ◽  
Author(s):  
Jacco J.A.J. Bastings ◽  
Hans M. van Eijk ◽  
Steven W. Olde Damink ◽  
Sander S. Rensen
Keyword(s):  
Amino Acids ◽  
Human Physiology ◽  
Amyotrophic Lateral Sclerosis ◽  
Human Body ◽  
Physiological Processes ◽  
Gut Barrier Function ◽  
Age Related ◽  
Health And Disease ◽  
Living Organisms ◽  
Lateral Sclerosis

d-amino acids, the enantiomeric counterparts of l-amino acids, were long considered to be non-functional or not even present in living organisms. Nowadays, d-amino acids are acknowledged to play important roles in numerous physiological processes in the human body. The most commonly studied link between d-amino acids and human physiology concerns the contribution of d-serine and d-aspartate to neurotransmission. These d-amino acids and several others have also been implicated in regulating innate immunity and gut barrier function. Importantly, the presence of certain d-amino acids in the human body has been linked to several diseases including schizophrenia, amyotrophic lateral sclerosis, and age-related disorders such as cataract and atherosclerosis. Furthermore, increasing evidence supports a role for d-amino acids in the development, pathophysiology, and treatment of cancer. In this review, we aim to provide an overview of the various sources of d-amino acids, their metabolism, as well as their contribution to physiological processes and diseases in man, with a focus on cancer.

A longer diagnostic interval is a risk for depression in amyotrophic lateral sclerosis

2014 ◽  
Vol 13 (4) ◽  
pp. 1019-1024 ◽  
Author(s):  
Jashelle Caga ◽  
Eleanor Ramsey ◽  
Anne Hogden ◽  
Eneida Mioshi ◽  
Matthew C. Kiernan
Keyword(s):  
Mental Health ◽  
Risk Factors ◽  
Amyotrophic Lateral Sclerosis ◽  
Depressive Symptoms ◽  
Psychiatric History ◽  
Related Risk ◽  
Health And Disease ◽  
Diagnostic Interval ◽  
Als Patients ◽  
Lateral Sclerosis

AbstractObjective:Recognizing depressive symptoms in patients with amyotrophic lateral sclerosis (ALS) remains problematic given the potential overlap with the normal psychological responses to a terminal illness. Understanding mental health and disease-related risk factors for depression is key to identifying psychological morbidity. The present study aimed to determine the prevalence of depressive symptoms in ALS and to explore mental health and disease-related risk factors for depression.Method:Structured medical and psychiatric history questionnaires and a validated depression scale (Depression, Anxiety, Stress Scale–21) were completed by 27 ALS patients (60% female; 59% limb onset; age 65.11 ± SE 2.21) prior to their initial review at a multidisciplinary clinic. Physical function was assessed with the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS–R).Results:At the time of initial assessment, 44% of patients had a previous psychiatric history, although the majority (62%) reported no symptoms of depression. The mean ALSFRS–R score was 37.78 ± SE 1.22, with an average diagnostic interval of 16.04 ± SE 2.39 months. Logistic regression analysis revealed that the length of the diagnostic interval alone predicted depressive symptoms (χ2(3, n = 26) = 9.21, Odds Ratio (OR) = 1.12, p < 0.05.Significance of Results:The illness experiences of ALS patients rather than established mental health risk factors influence the manifestation of depressive symptoms in the early stages of the disease, with clinical implications for the assessment and treatment of psychological morbidity. Patients with lengthy diagnostic intervals may be prime targets for psychological assessment and intervention, especially in the absence of ALS-specific tests and biomarkers.

scholarly journals Autophagic and endo-lysosomal dysfunction in neurodegenerative disease

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Bilal R. Malik ◽  
Daniel C. Maddison ◽  
Gaynor A. Smith ◽  
Owen M. Peters
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurological Disorders ◽  
Degradation Pathways ◽  
Genetic Pathways ◽  
Protein Clearance ◽  
Lysosomal Dysfunction ◽  
Broad Implication ◽  
Mechanistic Insight ◽  
Insight Into ◽  
Lateral Sclerosis

AbstractDue to their post-mitotic state, metabolic demands and often large polarised morphology, the function and survival of neurons is dependent on an efficient cellular waste clearance system both for generation of materials for metabolic processes and removal of toxic components. It is not surprising therefore that deficits in protein clearance can tip the balance between neuronal health and death. Here we discuss how autophagy and lysosome-mediated degradation pathways are disrupted in several neurological disorders. Both genetic and cell biological evidence show the diversity and complexity of vesicular clearance dysregulation in cells, and together may ultimately suggest a unified mechanism for neuronal demise in degenerative conditions. Causative and risk-associated mutations in Alzheimer’s disease, Frontotemporal Dementia, Amyotrophic Lateral Sclerosis, Parkinson’s disease, Huntington’s disease and others have given the field a unique mechanistic insight into protein clearance processes in neurons. Through their broad implication in neurodegenerative diseases, molecules involved in these genetic pathways, in particular those involved in autophagy, are emerging as appealing therapeutic targets for intervention in neurodegeneration.

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