Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuromuscular diseases occur in as many as 50% of patients infected with human immunodeficiency virus type 1 (HIV-1). All forms of neuromuscular disease have been reported, including axonal neuropathy, demyelinating neuropathy, mononeuropathy multiplex, polyradiculitis, ALS-like syndromes, disorders of neuromuscular transmission, myopathy, and toxic neuropathies due to medication side effects. Neuromuscular disease is often the presenting manifestation of HIV-1 infection. Infection with cytomegalovirus (CMV) is associated with different types of neuropathy including mononeuritis multiplex and polyradiculopathy. There is effective treatment for many of the associated disorders including chronic inflammatory demyelinating neuropathy, CMV-mediated neuropathies, and myopathy. Treatment of CMV-mediated mononeuropathy multiplex may be life saving. The different neuromuscular syndromes associated with different stages of HIV-1 infection may be due, in part, to different levels of immunocompetence.
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PMID:AAEM minimonograph #41: neuromuscular diseases associated with HIV-1 infection. 826 98

The increased oxidative stress induced by mutant SOD1 is associated with motor neuron degeneration in both human ALS and transgenic mice expressing mutant SOD1. Vascular endothelial growth factor (VEGF) is neurotrophic and also protects from hypoxia-induced neuronal injury. The potential role of VEGF in preventing mutant SOD1-mediated motor neuron cell death was examined using a mouse NSC34 motor neuron-like cell culture system. Infection with adenovirus containing mutant G93A-SOD1, but not vector control or wild-type SOD1, increased cellular oxidative stress and motor neuron-like cell death. However, NSC34 cells pretreated with VEGF displayed a dose-dependent resistance to oxidative damage from hydrogen peroxide, TNF-alpha, and mutant G93A-SOD1. VEGF activated both PI3-K and MAPK activities in mouse NSC34 motor neuron-like cells. Pharmacological inhibitors and constitutively active as well as dominant negative mutants of MAPK and PI3-K revealed that the protective effects of VEGF were mediated via the PI3-K activity, and that MAPK activation was not associated with NSC34 cell survival. Furthermore, VEGF-induced downstream Akt activation promoted motor neuron-like NSC34 cell survival in the presence of mutant G93A-SOD1. Thus, VEGF protected mouse NSC34 motor neuron-like cell death from mutant G93A-SOD1 effects via PI3-K/Akt activation.
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PMID:VEGF-induced activation of the PI3-K/Akt pathway reduces mutant SOD1-mediated motor neuron cell death. 1265 15

The available epidemiological data for amyotrophic lateral sclerosis (ALS) support an infectious etiology and lead us to propose a new hypothesis. We examined older epidemiological data concerning categories of the population with increased incidence (aged people, people living in rural areas, farmers, breeders), more recent epidemiological reports regarding Italian soccer players, AIDS patients, people living in highly polluted areas, and reports of cases of conjugal and pregnancy-associated ALS. The toxic and infectious hypotheses lead us to suggest a role for cyanobacteria in the production of endogenous beta-N-methylamino-L-alanine. Infection from a cyanobacterium, or another ubiquitous bacterium having similar characteristics, may be the missing clue to the etiology of ALS. We speculate that ubiquitous bacteria secreting toxic amino acids and "colonizing" tissues and organs in the human body might be the common element linking motor neuron diseases in Guam to sporadic ALS in the rest of the world.
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PMID:Sporadic amyotrophic lateral sclerosis as an infectious disease: a possible role of cyanobacteria? 1689 Mar 80

Neurological symptoms of patients suffering from neurodegenerative diseases such as Alzheimer's dementia (AD), Parkinson's disease (PD), or amyotrophic lateral sclerosis (ALS) often worsen during infections. We assessed the disease-modulating effects of recurrent systemic infections with the most frequent respiratory pathogen, Streptococcus pneumoniae, on the course of AD, PD, and ALS in mouse models of these neurodegenerative diseases [transgenic Tg2576 mice, (Thy1)-[A30P]alpha SYN mice, and Tg(SOD1-G93A) mice]. Mice were repeatedly challenged intraperitoneally with live S. pneumoniae type 3 and treated with ceftriaxone for 3 days. Infection caused an increase of interleukin-6 concentrations in brain homogenates. The clinical status of (Thy1)-[A30P]alpha SYN mice and Tg(SOD1-G93A) mice was monitored by repeated assessment with a clinical score. Motor performance was controlled by the tightrope test and the rotarod test. In Tg2576 mice, spatial memory and learning deficits were assessed in the Morris water maze. In none of the three mouse models onset or course of the disease as evaluated by the clinical tests was affected by the recurrent systemic infections performed. Levels of alpha-synuclein in brains of (Thy1)-[A30P]alpha SYN mice did not differ between infected animals and control animals. Plaque sizes and concentrations of A beta 1-40 and A beta 1-42 were not significantly different in brains of infected and uninfected Tg2576 mice. In conclusion, onset and course of disease in mouse models of three common neurodegenerative disorders were not influenced by repeated systemic infections with S. pneumoniae, indicating that the effect of moderately severe acute infections on the course of neurodegenerative diseases may be less pronounced than suspected.
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PMID:Recurrent systemic infections with Streptococcus pneumoniae do not aggravate the course of experimental neurodegenerative diseases. 1985 62

While peripheral immune access to the central nervous system (CNS) is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia) resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), tauopathies, and age-related macular degeneration (ARMD), are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the pathophysiology of several neurodegenerative diseases.
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PMID:Does neuroinflammation fan the flame in neurodegenerative diseases? 1991 31

A large group of diseases of unknown etiology, including leukemia, systemic lupus erythematosus, myelodysplastic disease, multiple sclerosis, amyotrophic lateral sclerosis, and rheumatoid arthritis, all present with some elements of immune system disturbance. The Ehrlichia/anaplasma (EA) are an obscure group of obligate parasitic intracellular pathogens that excrete intracellularly a substance called host transcriptional protein, which can alter transcription in cell division. Infection with EA may lead to changes in transcription in proliferating cells, such as those in the marrow, and alter the biology of the products such as T and B cells. Normally 60% of B cells produced in the marrow may be self reactive, but are eliminated before release from the marrow. Changes in transcription could allow self reactive cells to escape into the peripheral circulation and injure normal tissue, creating the dysfunctions which characterize the different immune system diseases and give them their separate identities. A number of studies previously published, and new information presented here, suggest that EA infections may be an underlying, undiagnosed cause for these and other immune system diseases. This hypothesis, long overlooked, has never been subjected to adequate, rigorous study sufficient to prove or disprove its truth. If so, patients may be treated with antibiotics, and marrow transplant manipulations already used in treatment of diseases such as lupus and leukemia may become more effective.
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PMID:Ehrlichia and bone marrow cells: could Ehrlichial infection explain the unsuspected etiology of some diseases of the immune system? 2166 95

Infection with the tick-borne spirochete, BORRELIA BURGDORFERI, affects the nervous system in well-defined ways. Accurate diagnostic tools and effective therapeutic regimens are now well established. Persistent misconceptions about (1) the role and interpretation of laboratory tests, (2) what is and is not evidence of nervous system infection, and (3) what constitutes an expected response to treatment have fostered widespread perceptions that this disease is highly controversial. Infection causes the classically described triad of meningitis, radiculoneuritis, and cranial neuritis; however, virtually every known neurologic disorder has been blamed on this infection. For most (multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer disease, Parkinson disease), evidence is scant, nonexistent, or coincidental. For some (cerebral vasculitis with stroke, optic neuritis) a few case reports suggest a rare possible causal link.
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PMID:Nervous system lyme disease: is there a controversy? 2196 48

Recent studies have shown that bacterial and viral infections are risk factors for various neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS), Multiple Sclerosis (MS), Alzheimer's disease (AD), and Lyme disease (LD). However, it is still controversial how the infections play a role in neurological diseases progression. Infections in central nervous system may lead multiple damages in infected and neighboring cells. The infection leads to the activation of inflammatory processes and host immune responses, which acts as defense mechanism and also causes damage to the host neuronal functions and viability. Several bacterial and viral pathogens have been reported for neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in combination with other factors, like aging, metabolic diseases and the genetic makeup of the host. We will focus in this review on the possible link between neurodegeneration and infections particularly Chlamydophila pneumoniae, Borrelia burgdorferi, Mycoplasma etc.
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PMID:Infectious Agents and Neurodegenerative Diseases: Exploring the Links. 2804 98