Amyotrophic lateral sclerosis - Wikipedia

 

als articles

Amyotrophic lateral sclerosis (ALS), also known as motor neurone disease (MND) or Lou Gehrig's disease, is a specific disease that causes the death of neurons controlling voluntary muscles. Some also use the term motor neuron disease for a group of conditions of which ALS is the most vjesnikws.gation: Riluzole, edaravone. ALS is a progressive disease, which means it gets worse over time. It affects nerves in your brain and spinal cord that control your muscles. As your muscles get weaker, it gets harder for you to. Sep 27,  · Amyotrophic lateral sclerosis (ALS), also referred to as "Lou Gehrig's disease," is a progressive motor neuron disease which leads to problems with muscle control and movement. There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or .


Amyotrophic Lateral Sclerosis | ALS | Lou Gehrig's disease | MedlinePlus


The etiology of ALS remains unknown. However, mutations of superoxide dismutase 1 have been known as the most common cause of FALS. In this study, we provide a comprehensive review of ALS. We cover all aspects of the disease including epidemiology, comorbidities, environmental risk factor, molecular mechanism, als articles, genetic factors, symptoms, diagnostic, treatment, als articles, and even the available supplement and management of ALS.

This will provide the reader with an advantage of receiving a broad range of information about the disease.

Amyotrophic lateral sclerosis ALS is a fatal motor neuron disorder that is, characterized by progressive loss of the upper and lower motor neurons LMNs at the spinal or bulbar level.

ALS is categorized in two forms. Most of the reviews about ALS focus on a specific area of the diseases such as molecular mechanism, treatment, als articles, diagnostic, etc.

This review will attempt to provide an up-to-date overview of all aspects of ALS. It will first cover the epidemiology als articles comorbidities of the disease, followed by known environmental risk factors such as smoking, chemical exposure, and radiation. Improving the understanding of ALS pathogenesis is critical in developing earlier diagnostic methods as well as proposing new effective treatments.

Thus, this review will present the most recent studies related to molecular mechanisms, genetics, Als articles symptoms, diagnostic examinations, and treatments. Furthermore, due to the fact that there has been only one Food and Drug Administration FDA approved drug for ALS treatment, this review will also address nutritional supplements, as well as respiratory and nutritional managements that help alleviating the symptoms.

This comprehensive study will inevitably lead to the better understanding of ALS and assist in extending the life expectancy associated with ALS by establishing a basis of knowledge that can be used to improve care. During 's, the number of reported cases of ALS was between 1. The mean age of onset of ALS als articles from 50 to 65 years with the median age of onset of 64 years old.

One hypothesis als articles the increased incidence in older population is related to the variation in care for these patients.

The age of onset for FALS is about a decade earlier than for sporadic cases. A possible relationship between ALS and sports participation has been proposed but not demonstrated.

In a cohort study of Italian professional football players, a severe increase in the incidence of ALS was found, als articles. Traumas to other als articles of the body were not associated with increased risk.

Retrospective cohort studies have shown that the incidence in certain concomitant diseases and comorbidities is significantly different in ALS-affected population in comparison to the general population.

German cohort studies examining comorbidities prior to diagnosis found that while cardiovascular risk factors were the most common comorbidities in ALS patients ALS patients had a significantly lower incidence of arterial hypertension With regards to comparing ALS types and their als articles time to patient comorbidities, only a difference in hypercholesterolemia incidence was seen when comparing bulbar onset to spinal onset Of the diseases most likely to be found in ALS patients prior to their diagnosis, a higher incidence in neurological disorders was noted when compared to the general population.

A history of depression Development of depression is one of the most common secondary symptoms associated with ALS. It is also possible that the administration of L-DOPA or the decreased levels of endogenous dopamine could offer an antioxidant protective effect in those susceptible to ALS, als articles, similar to that seen in multiple studies comparing ALS incidence and Vitamin E consumption.

Previous epidemiologic studies have suggested that ALS patients may have been exposed to environmental toxins. Cigarette smoke has been found to increase the probability of developing ALS through inflammation, oxidative stress, and neurotoxicity by heavy metals contained in cigarettes.

Furthermore, exhaled cigarette smoke contains formaldehyde which is associated with higher mortality rates in ALS als articles. Athletes have higher ALS risk compared to the general population; however, performing passive to robust physical activity has not shown an increased susceptibility of developing ALS. A possible explanation to the high risk of ALS incidence among athletes involves genetic profiles. Genetic profiles that promote physical fitness but not necessarily muscles strength could hold a proportional correlation between ALS and physical activity.

ALS has shown an association with exposure to agricultural chemicals such as pesticides, fertilizers, herbicides, insecticides, als articles, and formaldehyde. This study also found that among individuals with long period of exposure to formaldehyde, the ALS death rate was more than 2 times higher compared to those als articles one.

Among all the heavy metals that might be associated with ALS, lead exposure seems to be studied the most possibly due to the ALS-like symptoms experienced by people exposed to high concentrations of lead.

It is thought that lead's role in ALS has to do with its ability to substitute for calcium in intracellular reactions leading to damage the mitochondria, oxidative damage to neurons, and strengthen glutamate's als articles. When a group of researchers utilized an expert evaluation panel of industrial hygienists to examine self-reported occupational lead exposures, als articles, no association was found between ALS and lead exposure.

Laboratory studies have demonstrated that in vitro exposures to extremely lowfrequency electromagnetic waves generate a bigger quantity of cellular reactive oxygen than normal.

Previous studies state that consuming high level of glutamate and fat can have adverse effects on ALS patients while Omega 3 fatty acids, Vitamin E, als articles, and fiber can have defensive impact. Because of this, there may be a lack of information about the frequency and the amount of exposure to environmental factors. Also, this may also lead to the absence of biological markers in order to validate patient claims of exposure or pinpoint the possible action site.

Furthermore, due to ALS prolonged onset, it is difficult to isolate an als articles environmental factor. In order to identify or narrow down possible ALS risk factors, als articles, a cohort als articles utilizing mice as a control and experimental group could be appropriate.

Starting out with an emphasis on the most sought out factors smoking, heavy metals, physical activity, als articles, diet, radiation, and chemical exposure, als articles. In order to track changes accurately, a type of biomarker specific to the possible risk factor could be designed, to theoretically track the progression of the disease. Finding the molecular mechanisms by which motor neurons degenerate in ALS will aid in better understanding the disease's progress.

Also, elucidation of molecular mechanisms can yield insight als articles developing strategies for newer treatments, als articles. The molecular basis of ALS is an intriguing issue that warrants in-depth research and investigation, als articles. The most important proposed hypothesis for the pathogenesis of ALS includes glutamate excitotoxicity structural and functional abnormalities of mitochondria, impaired axonal structure or transport defects, and free radical-mediated oxidative stress.

Glutamate is synthesized in the presynaptic terminal. Uptake of glutamate into synaptic vesicles is facilitated by vesicular glutamate transporters. Upon release of the vesicle, glutamate is removed from the synaptic cleft by several glial and neuronal cell transporter proteins, such as excitatory amino acid transporters EAATs.

The motor cortex and spinal cord of ALS patients and transgenic SOD1 mouse model were found to have reduced astroglial glutamate transporter EAAT2, which leads to increased extracellular glutamate, over-stimulation of glutamate receptors, als articles, and excitotoxic neuronal degeneration.

These abnormalities included intron-retention and exon-skipping. In addition to glutamate excitotoxicity, mitochondrial dysfunction also plays an important role in the motor neuron degeneration. Mitochondria are membrane bound organelles that have a significant role in vital processes such as intracellular energy production, cellular respiration, calcium homeostasis, and control of apoptosis.

Functional defects and altered mitochondrial morphology such as fragmented network, als articles, swelling, and augmented cristae were found in soma and proximal axons of skeletal muscle and spinal motor neurons of ALS patients.

In the spinal cords of ALS patients, mutant Als articles is deposited on the cytoplasmic face of the outer membrane and matrix of mitochondria. Mitochondria act as the powerhouse of every cell by converting energy into ATP that is, als articles, essential for the metabolism of the cells.

The normal process of electron als articles chains is perturbed by the presence of mutant SOD1, causing less production of ATP. Some studies have demonstrated a decreased activity of respiratory chain complexes I and IV that are associated with defective energy metabolism.

In addition to energy homeostasis, als articles, another major function of mitochondria in neurons regards buffering cytosolic calcium levels, als articles. Thus, unraveling the relationship between aberrant mitochondria, als articles, calcium dysregulation, and neuronal death is critical for the understanding of ALS pathogenesis. Calcium is one of the most significant intracellular messengers that play an important role in the regulation of metabolic pathways, neuronal development, and als articles transmission.

Mutant SOD1 has been found to disrupt calcium homeostasis. Several studies have shown that intracellular calcium is misregulated in ALS patients, als articles. Regulating mitochondrial transport along axons is an essential task for the survival of neurons due to als articles mitochondria's key role in ATP generation, calcium buffering, and apoptotic signaling, als articles. Mitochondria are constantly being transported and docked at als articles same time in areas with high demand of ATP and calcium homeostasis such as growth cones, nodes of Ranvier, als articles, and synaptic terminals, als articles.

Several laboratories have identified disrupted als articles transport of mitochondria in ALS patients. Increased mitochondrial transport may slow axonal degeneration by delivering healthy mitochondria to axons while removing the damaged one from distal synapses. Finally, mutant SOD1 aggregates may also interfere with components of mitochondrial-dependent apoptotic machinery, such as B-cell lymphoma 2 Bcl-2which is a regulator protein that controls cell death. Motor neurons are highly polarized cells with long axons that can be more than a meter in length and are thus vulnerable to damage, als articles.

In addition to transmitting nerve impulses axons also transport organelles, RNA, proteins, lipids, and other cell parts to the axonal compartments. Moving als articles the soma is called retrograde and is performed by cytoplasmic dynein molecular motors while moving toward the synaptic structures at the neuromuscular junction is an anterograde transport and is conducted by microtubule-dependent kinesin, als articles.

Axonal transport in ALS patients is compromised. Dysregulation of axonal transport and the axonal compartment play a critical role in the pathophysiology of ALS. In several experiment with mutant SOD1 mice, loss of neurotrophic signaling and defective axonal transport were observed early in the disease process.

Several pathways may be responsible for the impaired axonal transport in cases with mutant SOD1. Some of the most important mechanisms involve defective mitochondrial function or energy depletion, disruption of kinesin function by tumor necrosis factor, als articles, and excitotoxic damage by glutamate. This leads to further hindrance of axonal transport and eventual motor neuron death.

Reactive oxygen species ROS or free radicals form as natural byproducts of the normal metabolism of oxygen. The term oxidative stress is used to define a disturbance in the balance between the production ROS and cell's antioxidant defenses, als articles.

Increased oxidative damage has been reported in ALS case biopsies and altered redox reactions were among the earliest theories of how mutant SOD1 could cause cytotoxicity, als articles. SOD1 is a major antioxidant protein, thus a mutation in this gene could cause cytotoxicity. Elevation of free radicals and increased oxidative damage were found in CSF, serum, als articles, and urine samples of ALS patients. Genetic testing can als articles used to differentiate inherited versus sporadic ALS and also to rule out als articles diseases that clinically mimic ALS.

OPTN is a gene involved in open-angle glaucoma, where a mutation in this gene eradicates the inhibition of nuclear factor kappa-beta activation, changing the distribution of OPTN in the cytoplasm. The lifetime risk of ALS is for women and for men.

Genome-wide association studies GWAS has allowed for the identification of common variables that are coupled to this disease. Family aggregation studies for SALS patients have shown that many people who have common als articles disorders also have ALS, possibly indicating the presence of a susceptible gene that could be responsible for increasing neurodegeneration in kindreds.

ALS patients experience localized muscle weakness that begins distally or proximally in their upper and lower limbs.

Usually, the onset symptoms are asymmetric and develop in progressive generalized weakness and wasting of the muscles. The majority of the patients develop bulbar and respiratory symptoms and spasticity, als articles, which affects manual dexterity and gait.

Speech disturbances tend to appear before the development of dysphagia for solids and liquids. Symptoms characteristic of limb-onset can develop simultaneously with bulbar symptoms occurring within 1—2 years. Patients with bulbar symptoms suffer from sialorrhea excessive drooling due to difficulty of swallowing saliva and minor bilateral lower facial weakness from UMN damage.

 

Amyotrophic lateral sclerosis (ALS): Causes, symptoms, and treatment

 

als articles

 

ALS News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. ALS is a progressive disease, which means it gets worse over time. It affects nerves in your brain and spinal cord that control your muscles. As your muscles get weaker, it gets harder for you to. Sep 27,  · Amyotrophic lateral sclerosis (ALS), also referred to as "Lou Gehrig's disease," is a progressive motor neuron disease which leads to problems with muscle control and movement. There are various types of ALS that are distinguished by symptoms and, in some cases, genetic cause. Early symptoms may include muscle twitching, cramping, stiffness, or weakness, slurred speech, and/or .