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)

Electron dense material was observed in the extracellular spaces between adjacent components of the Schmidt-Lanterman clefts and between lateral loops at the paranodes in some of the heavily myelinated fibers of the anterior roots and peripheral nerves of a patient with amyotrophic lateral sclerosis. Similar deposits were seen in tissue derived from patients who died with no neurological disease. These deposits were also present in the extracellular spaces of the endoneurium and beneath the outer cytoplasmic collar of the sheath, but did not penetrate the intraperiod line of the compact myelin or the periaxonal space and the lateral loops tended to remain in contact with the axon. The findings suggest that a pathway exists between the extracellular spaces outside the sheath to the innermost portion of the sheath but that the periaxonal space is resistant to the penetration of the extraneous material.
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PMID:The permeability of the extracellular spaces at the Schmidt-Lanterman clefts and paranodes in peripheral myelin sheaths. 713 14

Mutations in superoxide dismutase (SOD1) are causative for inherited amyotrophic lateral sclerosis. A proportion of SOD1 mutant protein is misfolded onto the cytoplasmic face of mitochondria in one or more spinal cord cell types. By construction of mice in which mitochondrially targeted enhanced green fluorescent protein is selectively expressed in motor neurons, we demonstrate that axonal mitochondria of motor neurons are primary in vivo targets for misfolded SOD1. Mutant SOD1 alters axonal mitochondrial morphology and distribution, with dismutase active SOD1 causing mitochondrial clustering at the proximal side of Schmidt-Lanterman incisures within motor axons and dismutase inactive SOD1 producing aberrantly elongated axonal mitochondria beginning pre-symptomatically and increasing in severity as disease progresses. Somal mitochondria are altered by mutant SOD1, with loss of the characteristic cylindrical, networked morphology and its replacement by a less elongated, more spherical shape. These data indicate that mutant SOD1 binding to mitochondria disrupts normal mitochondrial distribution and size homeostasis as early pathogenic features of SOD1 mutant-mediated ALS.
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PMID:Misfolded SOD1 associated with motor neuron mitochondria alters mitochondrial shape and distribution prior to clinical onset. 2177 68