scholarly journals Destination Amyotrophic Lateral Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Matt Keon ◽  
Benjamin Musrie ◽  
Marcel Dinger ◽  
Samuel E. Brennan ◽  
Jerran Santos ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Functional Convergence ◽  
Progressive Degeneration ◽  
Fundamental Dimension ◽  
Multiple Levels ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis ◽  
Philosophical Understanding

Amyotrophic Lateral Sclerosis (ALS) is a prototypical neurodegenerative disease characterized by progressive degeneration of motor neurons both in the brain and spinal cord. The constantly evolving nature of ALS represents a fundamental dimension of individual differences that underlie this disorder, yet it involves multiple levels of functional entities that alternate in different directions and finally converge functionally to define ALS disease progression. ALS may start from a single entity and gradually becomes multifactorial. However, the functional convergence of these diverse entities in eventually defining ALS progression is poorly understood. Various hypotheses have been proposed without any consensus between the for-and-against schools of thought. The present review aims to capture explanatory hierarchy both in terms of hypotheses and mechanisms to provide better insights on how they functionally connect. We can then integrate them within a common functional frame of reference for a better understanding of ALS and defining future treatments and possible therapeutic strategies. Here, we provide a philosophical understanding of how early leads are crucial to understanding the endpoints in ALS, because invariably, all early symptomatic leads are underpinned by neurodegeneration at the cellular, molecular and genomic levels. Consolidation of these ideas could be applied to other neurodegenerative diseases (NDs) and guide further critical thinking to unveil their roadmap of destination ALS.

scholarly journals How Degeneration of Cells Surrounding Motoneurons Contributes to Amyotrophic Lateral Sclerosis

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2550
Author(s):  
Roxane Crabé ◽  
Franck Aimond ◽  
Philippe Gosset ◽  
Frédérique Scamps ◽  
Cédric Raoul
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Glial Cells ◽  
Neurological Disorder ◽  
Cellular Network ◽  
Motor System ◽  
Progressive Degeneration ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by the progressive degeneration of upper and lower motoneurons. Despite motoneuron death being recognized as the cardinal event of the disease, the loss of glial cells and interneurons in the brain and spinal cord accompanies and even precedes motoneuron elimination. In this review, we provide striking evidence that the degeneration of astrocytes and oligodendrocytes, in addition to inhibitory and modulatory interneurons, disrupt the functionally coherent environment of motoneurons. We discuss the extent to which the degeneration of glial cells and interneurons also contributes to the decline of the motor system. This pathogenic cellular network therefore represents a novel strategic field of therapeutic investigation.

scholarly journals New perspectives on cytoskeletal dysregulation and mitochondrial mislocalization in amyotrophic lateral sclerosis

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Frances Theunissen ◽  
Phillip K. West ◽  
Samuel Brennan ◽  
Bojan Petrović ◽  
Kosar Hooshmand ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Retrograde Transport ◽  
Cytoskeletal Proteins ◽  
Charcot Marie Tooth Disease ◽  
Mitochondrial Homeostasis ◽  
Axonal Projections ◽  
Cytoskeletal Network ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective, early degeneration of motor neurons in the brain and spinal cord. Motor neurons have long axonal projections, which rely on the integrity of neuronal cytoskeleton and mitochondria to regulate energy requirements for maintaining axonal stability, anterograde and retrograde transport, and signaling between neurons. The formation of protein aggregates which contain cytoskeletal proteins, and mitochondrial dysfunction both have devastating effects on the function of neurons and are shared pathological features across several neurodegenerative conditions, including ALS, Alzheimer's disease, Parkinson's disease, Huntington’s disease and Charcot-Marie-Tooth disease. Furthermore, it is becoming increasingly clear that cytoskeletal integrity and mitochondrial function are intricately linked. Therefore, dysregulations of the cytoskeletal network and mitochondrial homeostasis and localization, may be common pathways in the initial steps of neurodegeneration. Here we review and discuss known contributors, including variants in genetic loci and aberrant protein activities, which modify cytoskeletal integrity, axonal transport and mitochondrial localization in ALS and have overlapping features with other neurodegenerative diseases. Additionally, we explore some emerging pathways that may contribute to this disruption in ALS.

scholarly journals Death Receptors in the Selective Degeneration of Motoneurons in Amyotrophic Lateral Sclerosis

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Julianne Aebischer ◽  
Nathalie Bernard-Marissal ◽  
Brigitte Pettmann ◽  
Cédric Raoul
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Immune Cells ◽  
Microglial Activation ◽  
Death Receptors ◽  
Strong Body ◽  
Als Patients ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

While studies on death receptors have long been restricted to immune cells, the last decade has provided a strong body of evidence for their implication in neuronal death and hence neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). ALS is a fatal paralytic disorder that primarily affects motoneurons in the brain and spinal cord. A neuroinflammatory process, associated with astrocyte and microglial activation as well as infiltration of immune cells, accompanies motoneuron degeneration and supports the contribution of non-cell-autonomous mechanisms in the disease. Hallmarks of Fas, TNFR, LT-βR, and p75NTR signaling have been observed in both animal models and ALS patients. This review summarizes to date knowledge of the role of death receptors in ALS and the link existing between the selective loss of motoneurons and neuroinflammation. It further suggests how this recent evidence could be included in an ultimate multiapproach to treat patients.

Role of transition metals in the pathogenesis of amyotrophic lateral sclerosis

2008 ◽  
Vol 36 (6) ◽  
pp. 1322-1328 ◽  
Author(s):  
Willianne I.M. Vonk ◽  
Leo W.J. Klomp
Keyword(s):  
Spinal Cord ◽  
Amyotrophic Lateral Sclerosis ◽  
Superoxide Dismutase ◽  
Transition Metals ◽  
Motor Neurons ◽  
Neurodegenerative Disorder ◽  
Sod1 Gene ◽  
Brain And Spinal Cord ◽  
Lateral Sclerosis

ALS (amyotrophic lateral sclerosis) is a devastating progressive neurodegenerative disorder resulting in selective degeneration of motor neurons in brain and spinal cord and muscle atrophy. In approx. 2% of all cases, the disease is caused by a mutation in the Cu,Zn-superoxide dismutase (SOD1) gene. The transition metals zinc and copper regulate SOD1 protein stability and activity, and disbalance of the homoeostasis of these metals has therefore been implicated in the pathogenesis of ALS. Recent data strengthen the hypothesis that these transition metals are excellent potential targets to develop an effective therapy for ALS.

scholarly journals Organization of acetylcholine containing structures in the cranial motor nuclei of the rhombencephalon of the pig

2008 ◽  
Vol 52 (No. 7) ◽  
pp. 293-300 ◽  
Author(s):  
M. Zalecki ◽  
J. Calka ◽  
M. Lakomy
Keyword(s):  
Spinal Cord ◽  
Cholinergic System ◽  
Immunohistochemical Method ◽  
Motor Nucleus ◽  
Progressive Degeneration ◽  
Dorsal Motor Nucleus ◽  
Motor Nuclei ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

We explored the immunoreactivity of choline acetyltransferase (ChAT) in the cranial nerve motor nuclei of the porcine rhombencephalon to reveal the cholinergic nature of these regions. In our experiments we used an immunohistochemical method for the visualization of all acetylcholine-containing structures. All studied motor nuclei contained ChAT-positive cell bodies and fibres, but the intensity of staining differed between the nuclei. Furthermore, characteristic ChAT-immunoreactive bouton-like structures, which are known to be synaptic terminals of the cholinergic system, were observed in the borders of all studied regions. The localization of ChAT-positive “boutons” in the neuropil of the examined nuclei and their proximity to stained perikarya allowed us to differentiate two groups of motor nuclei in the rhombencephalon of the pig: (a) Nuclei containing ChAT-positive bouton-like structures dispersed in the neuropil, often establishing contacts with the stained cell bodies − motor trigeminal, abducent, facial, ambiguous and hypoglossal nuclei. (b) Nuclei in which characteristic boutons were dispersed among the ChAT-positive cells, but were devoid of any contact with perikarya − dorsal motor nucleus of the vagus nerve. These results provide new data on the porcine central nervous system and could be useful in further experiments on amyotrophic lateral sclerosis (ALS) − the disease that results in the progressive degeneration of motoneurons in the brain and spinal cord.

scholarly journals A review: Management of motor neuron diseases

2022 ◽  
Vol 7 (4) ◽  
pp. 292-294
Author(s):  
Aarti Chopra ◽  
Ravi Kumar ◽  
Girendra Kumar Gautam
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neuron ◽  
Motor Neurons ◽  
Age At Onset ◽  
Motor Neuron Diseases ◽  
Progressive Degeneration ◽  
Review Management ◽  
The Central Nervous System ◽  
Lateral Sclerosis

Motor neuron diseases are a group of chronic sporadic and hereditary neurological disorders characterized by progressive degeneration of motor neurons. These might affect the upper motor neurons, lower motor neurons, or both. The prognosis of the motor neuron disease depends upon the age at onset and the area of the central nervous system affected. Amyotrophic lateral sclerosis (ALS) has been documented to be fatal within three years of onset. This activity focuses on amyotrophic lateral sclerosis as the prototype of MND, which affects both the upper and the lower motor neurons and discusses the role of inter-professional team in the differential diagnosis, evaluation, treatment, and prognostication. It also discusses various other phenotypes of MND with an emphasis on their distinguishing features in requisite detail.

scholarly journals Amyotrophic Lateral Sclerosis and Metabolomics: Clinical Implication and Therapeutic Approach

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Alok Kumar ◽  
Devlina Ghosh ◽  
R. L. Singh
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Neurodegenerative Disorders ◽  
Metabolic Profile ◽  
Body Fluids ◽  
Fast Progression ◽  
Progression Of Disease ◽  
Als Patients ◽  
The Brain ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is one of the most common motor neurodegenerative disorders, primarily affecting upper and lower motor neurons in the brain, brainstem, and spinal cord, resulting in paralysis due to muscle weakness and atrophy. The majority of patients die within 3–5 years of symptom onset as a consequence of respiratory failure. Due to relatively fast progression of the disease, early diagnosis is essential. Metabolomics offer a unique opportunity to understand the spatiotemporal metabolic crosstalks through the assessment of body fluids and tissue. So far, one of the most challenging issues related to ALS is to understand the variation of metabolites in body fluids and CNS with the progression of disease. In this paper we will review the changes in metabolic profile in response to disease progression condition and also see the therapeutic implication of various drugs in ALS patients.

scholarly journals Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis

2020 ◽  
Vol 14 (1) ◽  
pp. 29
Author(s):  
HaEun Cho ◽  
Surabhi Shukla
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Treatment Option ◽  
Unsaturated Fatty Acids ◽  
Neuronal Damage ◽  
Cognitive Difficulties ◽  
Clinical Presentations ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that leads to a loss of muscle control due to nerve cells being affected in the brain and spinal cord. Some of the common clinical presentations of ALS include weakness of muscles, changes in behavior, dysfunction in speech, and cognitive difficulties. The cause of ALS is uncertain, but through several studies, it is known that mutations in SOD1 or C9orf72 genes could play a role as a factor of ALS. In addition, studies indicate that an excessive amount of free radicals, the reactive oxygen species (ROS), leads to neuronal damage by the peroxidation of unsaturated fatty acids in the neuronal cells. Edaravone, the newly approved antioxidant drug for ALS, halts the progression of ALS in the early stages through its cytoprotective effect and protects the nerves by reducing ROS. In this review, different aspects of ALS will be discussed, including its pathology, genetic aspect, and diagnosis. This review also focuses on edaravone as a treatment option for ALS, its mechanism of action, and its pharmacological properties. Clinical trials and adverse effects of edaravone and care for ALS patient are also discussed.

Potential skin involvement in ALS: revisiting Charcot’s observation – a review of skin abnormalities in ALS

2017 ◽  
Vol 28 (5) ◽  
pp. 551-572 ◽  
Author(s):  
Bastien Paré ◽  
François Gros-Louis
Keyword(s):  
Motor Neurons ◽  
Skin Changes ◽  
Embryonic Origin ◽  
Skin Abnormalities ◽  
Als Patients ◽  
The 19Th Century ◽  
Brain And Spinal Cord ◽  
The Brain ◽  
Lateral Sclerosis

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease affecting motor neurons of the brain and spinal cord, leading to progressive paralysis and death. Interestingly, many skin changes have been reported in ALS patients, but never as yet fully explained. These observations could be due to the common embryonic origin of the skin and neural tissue known as the ectodermal germ layer. Following the first observation in ALS patients’ skin by Dr Charcot in the 19th century, in the absence of bedsores unlike other bedridden patients, other morphological and molecular changes have been observed. Thus, the skin could be of interest in the study of ALS and other neurodegenerative diseases. This review summarizes skin changes reported in the literature over the years and discusses about a novelin vitroALS tissue-engineered skin model, derived from patients, for the study of ALS.

Sign in / Sign up

Export Citation Format

Share Document