RESUMEN
Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron degenerative disease whose etiology and pathogenesis remain poorly understood. Most cases of ALS ( approximately 90%) are sporadic (SALS), occurring in the absence of genetic associations. Approximately 20% of familial ALS (FALS) cases are due to known mutations in the copper, zinc superoxide dismutase (SOD1) gene. Molecular evidence for a common pathogenesis of SALS and FALS has remained elusive. Here we use covalent chemical modification to reveal an attribute of spinal cord SOD1 common to both SOD1-linked FALS and SALS, but not present in normal or disease-affected tissues from other neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's diseases and spinal muscular atrophy, a non-ALS motor neuron disease. Biotinylation reveals a 32-kDa, covalently cross-linked SOD1-containing protein species produced not only in FALS caused by SOD1 mutation, but also in SALS. These studies use chemical modification as a novel tool for the detection of a disease-associated biomarker. Our results identify a shared molecular event involving a known target gene and suggest a common step in the pathogenesis between SALS and FALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/enzimología , Superóxido Dismutasa/metabolismo , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/patología , Esclerosis Amiotrófica Lateral/congénito , Esclerosis Amiotrófica Lateral/patología , Antígenos/inmunología , Autopsia , Biotina/química , Demencia/enzimología , Demencia/patología , Susceptibilidad a Enfermedades , Humanos , Peso Molecular , Atrofia Muscular Espinal/enzimología , Atrofia Muscular Espinal/patología , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/patología , Superóxido Dismutasa/química , Superóxido Dismutasa/inmunología , Superóxido Dismutasa-1RESUMEN
Like many hydrophobic organic compounds, 3,3'-dichlorobenzidine (DCB) partitions preferentially to (sediment) particles in lake systems. As such, the behavior of DCB in these systems is substantially affected by the movement of sediments. A field investigation of DCB distribution in sediments of Lake Macatawa (Holland, MI, USA) was initiated. The pattern of DCB distribution within the lake was found to display an oscillatory pattern that was consistent with a wind-driven mechanism of sediment transport. Numerical modeling of seiching behavior supported the hypothesized importance of this mechanism of sediment transport and redistribution. The dynamic behavior of sediment-associated DCB within Lake Macatawa seems to be strongly influenced by phenomena that are common to many freshwater estuaries. As such, the behavior of this system is expected to represent a reasonable model of the dynamic behavior of hydrophobic contaminants in other freshwater estuaries.