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)

At the present time, it seems unlikely that progressive neurodegenerative diseases, such as ALS, Parkinson's disease, and dementia of the Alzheimer type, are triggered by environmental agents with excitotoxic potential. These include excitotoxic agents that behave as glutamate agonists or disrupt energy metabolism: both types elicit permanent but self-limiting neuronal diseases with patterns of neuronal deficit that reflect selective chemical exposure (MPP+ and parkinsonism), differential susceptibility to energy dysmetabolism (NPA and dystonia), or the distribution of glutamate-receptors (domoic acid and memory loss). If environmental agents play an etiologic role in progressive neurodegenerative diseases, they are likely to target a critical, irreplaceable neuronal molecule that is required to maintain long-term neuronal integrity.
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PMID:Are human neurodegenerative disorders linked to environmental chemicals with excitotoxic properties? 132 79

The striatum, together with the hippocampus, is one of the most vulnerable regions in the brain. Recently, genetic abnormalities or mutations have been linked to various neurodegenerative diseases, that is, Huntington's disease, Alzheimer's disease, amyotrophic lateral sclerosis (ALS), etc., but the processes from genetic abnormality to the final phenotypic expression are not well understood. Disturbances in energy metabolism especially in mitochondrial energy compromise could facilitate genetic abnormalities and enhance neuronal cell death. Here, we report that the striatum is the most vulnerable brain region to systemic intoxication with 3-nitropropionic acid (3-NPA), an inhibitor of succinate dehydrogenase inducing energy compromise. We hypothesize that the striatum-specific lesion by 3-NPA is due to cummulative insults characteristic to the striatum including glutamatergic excitotoxicity, dopaminergic toxicity, vulnerability of the lateral striatal artery and high activity in the glutamate-transporter. The former two are extravascular in origin while the latter two are intra-/perivascular. We also discuss the possibility that a high turnover rate in metabolism of nitric oxide (NO) might underlie the vulnerability of the lateral striatal artery. We posit that systemic intoxication with 3-NPA offers a good animal model to investigate the pathophysiology of neuronal/glial cell death, neurodegenerative disease, dysfunction of the blood-brain barrier (BBB), neuroimmune disorders, and stroke.
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PMID:The striatum is the most vulnerable region in the brain to mitochondrial energy compromise: a hypothesis to explain its specific vulnerability. 1075 30