The Links between ALS and NF-kB

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease wherein motor neuron degeneration leads to muscle weakness, progressive paralysis, and death within 3-5 years of diagnosis. Currently, the cause of ALS is unknown but, as with several neurodegenerative diseases, the potential role of neuroinflammation has become an increasingly popular hypothesis in ALS research. Indeed, upregulation of neuroinflammatory factors have been observed in both ALS patients and animal models. One such factor is the inflammatory inducer NF-kB. Besides its connection to inflammation, NF-kB activity can be linked to several genes associated to familial forms of ALS, and many of the environmental risk factors of the disease stimulate NF-kB activation. Collectively, this has led many to hypothesize that NF-kB proteins may play a role in ALS pathogenesis. In this review, we discuss the genetic and environmental connections between NF-kB and ALS, as well as how this pathway may affect different CNS cell types, and finally how this may lead to motor neuron degeneration.

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A potential role for the p75 low-affinity neurotrophin receptor in spinal motor neuron degeneration in murine and human amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders ◽

10.1080/146608201753275463 ◽

2001 ◽

Vol 2 (3) ◽

pp. 127-134 ◽

Cited By ~ 73

Author(s):

KS Lowry ◽

SS Murray ◽

CA McLean ◽

P Talman ◽

S Mathers ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Potential Role ◽

Neurotrophin Receptor ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Spinal Motor Neuron ◽

Spinal Motor ◽

Lateral Sclerosis

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The role of D-serine and glycine as co-agonists of NMDA receptors in motor neuron degeneration and amyotrophic lateral sclerosis (ALS)

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2014.00010 ◽

2014 ◽

Vol 6 ◽

Cited By ~ 31

Author(s):

Praveen Paul ◽

Jackie de Belleroche

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Nmda Receptors ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Lateral Sclerosis

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Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis

Nutrients ◽

10.3390/nu13113804 ◽

2021 ◽

Vol 13 (11) ◽

pp. 3804

Author(s):

Polina S. Goncharova ◽

Tatiana K. Davydova ◽

Tatiana E. Popova ◽

Maxim A. Novitsky ◽

Marina M. Petrova ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Motor Neurons ◽

Randomized Clinical Trials ◽

Progression Rate ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Vitamin B9 ◽

Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

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Excitotoxicity and genetics of amyotrophic lateral sclerosis: effects of intracellular calcium accumulation on proteins encoded by the major genes underlying the disease

10.21203/rs.3.rs-220372/v1 ◽

2021 ◽

Author(s):

Giovanni DE MARCO ◽

Annarosa Lomartire ◽

Umberto Manera ◽

Antonio Canosa ◽

Maurizio Grassano ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Cell Types ◽

Motor Neuron Degeneration ◽

Neuron Degeneration ◽

Incurable Disease ◽

Intracellular Ca ◽

Neuron Damage ◽

Proteolytic Action ◽

Lateral Sclerosis

Abstract The aetiology of Amyotrophic Lateral Sclerosis (ALS), a fatal and incurable disease caused by motor neuron degeneration, is still poorly understood. The discovery of genetic forms of ALS helped to shed light on the mechanisms underlying this pathology, but also showed how complex these mechanisms are. Excitotoxicity is one of the processes strongly suspected to play a role in motor neuron degeneration in ALS. This process consists in neuron damage due to excessive intake of calcium ions (Ca2+) by the cell. This study aims to find a relationship between the proteins coded by the most relevant genes associated with ALS and excitotoxicity. In detail, the profile of eight proteins (TDP-43, C9ORF72, p62/SQSTM1, matrin3, VCP, FUS, SOD1 and profilin-1), was analysed in three different cell types induced to raise their cytoplasmic amount of Ca2+. Intracellular Ca2+ accumulation causes a significant decrease in the levels of TDP-43, C9ORF72, matrin3, VCP, FUS, SOD1 and profilin-1 and an increase in p62/SQSTM1. These events are associated to the proteolytic action of two proteases, calpains and caspases, as well as to the activation of autophagy, a process responsible for the degradation and recycling of cytoplasmic components. Interestingly, Ca2+ appears to both favour and hinder autophagy. The discovery of when Ca2+ levels become toxic for the cell, as well as understanding why the physiological processes of calpain proteolysis and autophagy become pathological, may elucidate the mechanisms responsible for ALS and help discover new therapeutic targets.

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