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

Sporadic amyotrophic lateral sclerosis (ALS) is one of the most devastating neurological diseases; most patients die within 3 to 4 years after symptom onset. Oxidative stress is a disturbance in the pro-oxidative/antioxidative balance favoring the pro-oxidative state. Autopsy and laboratory studies in ALS indicate that oxidative stress plays a major role in motor neuron degeneration and astrocyte dysfunction. Oxidative stress biomarkers in cerebrospinal fluid, plasma, and urine are elevated, suggesting that abnormal oxidative stress is generated outside of the central nervous system. Our review indicates that agricultural chemicals, heavy metals, military service, professional sports, excessive physical exertion, chronic head trauma, and certain foods might be modestly associated with ALS risk, with a stronger association between risk and smoking. At the cellular level, these factors are all involved in generating oxidative stress. Experimental studies indicate that a combination of insults that induce modest oxidative stress can exert additive deleterious effects on motor neurons, suggesting that multiple exposures in real-world environments are important. As the disease progresses, nutritional deficiency, cachexia, psychological stress, and impending respiratory failure may further increase oxidative stress. Moreover, accumulating evidence suggests that ALS is possibly a systemic disease. Laboratory, pathologic, and epidemiologic evidence clearly supports the hypothesis that oxidative stress is central in the pathogenic process, particularly in genetically susceptive individuals. If we are to improve ALS treatment, well-designed biochemical and genetic epidemiological studies, combined with a multidisciplinary research approach, are needed and will provide knowledge crucial to our understanding of ALS etiology, pathophysiology, and prognosis.
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PMID:Clinical perspective on oxidative stress in sporadic amyotrophic lateral sclerosis. 2379 33

Immune cell infiltration to the brain's territory was considered for decades to reflect a pathological process in which immune cells attack the central nervous system (CNS); such a process is observed in the inflammatory autoimmune disease, multiple sclerosis (MS). As neuroinflammatory processes within the CNS parenchyma are also common to other CNS pathologies, regardless of their etiology, including neurodegenerative disorders such as Alzheimer's disease (AD) and Amyotrophic lateral sclerosis (ALS), these pathologies have often been compared to MS, a disease that benefits from immunosuppressive therapy. Yet, over the last decade, it became clear that autoimmunity has a bright side, and that it plays a pivotal role in CNS repair following damage. Specifically, autoimmune T cells were found to facilitate CNS healing processes, such as in the case of sterile mechanical injuries to the brain or the spinal cord, mental stress, or biochemical insults. Even more intriguingly, autoimmune T cells were found to be involved in supporting fundamental processes of brain functional integrity, such as in the maintenance of life-long brain plasticity, including spatial learning and memory, and neurogenesis. Importantly, autoimmune T cells are part of a cellular network which, to operate efficiently and safely, requires tight regulation by other immune cell populations, such as regulatory T cells, which are indispensable for maintenance of immunological self-tolerance and homeostasis. Here, we suggest that dysregulation of the balance between peripheral immune suppression, on one hand, and protective autoimmunity, on the other, is an underlying mechanism in the emergence and progression of the neuroinflammatory response associated with chronic neurodegenerative diseases and brain aging. Mitigating chronic neuroinflammation under these conditions necessitates activation, rather than suppression, of the peripheral immune response directed against self. Accordingly, we propose that fighting off acute and chronic neurodegenerative conditions requires breaking peripheral immune tolerance to CNS self-antigens, in order to boost protective autoimmunity. Nevertheless, the optimal approach to fine tune such immune response must be individually explored for each condition.
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PMID:Breaking peripheral immune tolerance to CNS antigens in neurodegenerative diseases: boosting autoimmunity to fight-off chronic neuroinflammation. 2519 10

Major depressive disorder (MDD) is one of the most prevalent and life-threatening forms of mental illnesses affecting elderly people and has been associated with poor cognitive function. Recent evidence suggests a strong relationship between MDD and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), as well as natural processes of aging. Changes in the neuroplasticity, morphology, and neurotransmission in the brain are seem to be associated to both, MDD and neurodegenerative diseases. In addition, there is evidence that psychological stress and MDD are associated with molecular and cellular signs of accelerated aging. This review will highlight the relationship between MDD, the aging process, and neurodegenerative diseases, emphasizing the neurochemical processes involved.
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PMID:Neurochemical correlation between major depressive disorder and neurodegenerative diseases. 2737 Sep 38

Psychological stress has been suggested to be relevant to the pathogenesis of neurodegenerative disorders, possibly via the generation of oxygen free radicals. We therefore sought to determine whether people with amyotrophic lateral sclerosis (ALS) had been subjected to more potentially stressful life events or occupations than controls, and whether they had differences in resilience or trait anxiety that would moderate their responses to these stressors. An online anonymous multilingual questionnaire was used to collect data on significant life events from people with and without ALS, using items from a modified Social Readjustment Rating Scale and from self-described significant events, which were combined to create a Life Events Inventory. Inventory scores were subdivided into 0-20 years and 21-40 years age ranges, and for the preceding 2, 5 and 10 years. Respondents also rated levels of stress experienced during different occupations. Resilience was measured using the Connor-Davidson Resilience Scale, and trait anxiety with a modified Geriatric Anxiety Inventory. Scores were compared using nonparametric statistics. Data from 400 ALS (251 male, 149 female) and 450 control (130 male, 320 female) respondents aged 40 years and over showed that Life Events Inventory scores were similar in male ALS respondents and controls, but lower in female ALS respondents than female controls for the preceding 5-year and 10-year periods. Occupational stress did not differ between ALS respondents and controls. Both male and female ALS respondents had higher resilience scores than controls. Anxiety scores did not differ between ALS and control groups. In conclusion, people with ALS reported no raised levels of potentially stressful premorbid life events or occupational stress, and did not have reduced levels of resilience, or increased levels of anxiety, that would augment the deleterious effects of stressors. On the contrary, ALS respondents had higher resilience than controls, though this conclusion relies on ALS respondents recalling their premorbid status. These results do not support the hypothesis that psychological stress from significant life events or occupational stress plays a role in the pathogenesis of ALS.
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PMID:Is psychological stress a predisposing factor for amyotrophic lateral sclerosis (ALS)? An online international case-control study of premorbid life events, occupational stress, resilience and anxiety. 3024 Apr 31