Amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), also known as 'Lou Gehrig's disease' (named after a baseball player who died from ALS in 1941) was initially described by Charcot in 1869. This neurological disease is manifested by degeneration of motor neurones located in cortex, brain stem and spinal cord. Clinically the ALS appears in the form of progressive paralysis and muscle atrophy. One of the important determinants of neuronal death in ALS is represented by deficient glutamate clearance, and as a consequence, excitotoxic neuronal damage. Reduced glutamate clearance is associated with a disappearance of astroglial glutamate transporter EAAT2 in the affected brain areas. Experimental genetic deletion of EAAT2 (GLT-1) in mice led to a pronounced loss of motor neurones thus mimicking ALS. The disappearance of EAAT2 in human astroglia in sporadic ALS is the consequence of gene failure and may result from aberrant RNA splicing, exon skipping and intron retention. In the hereditary form of ALS the down-regulation of glutamate transporter can result from oxidative damage; patients carry mutations in a gene that encodes Cu/Zn superoxide dismutase (SOD1); the latter being an enzyme that converts superoxide radicals to hydrogen peroxide. Aberrant SOD1 results in an increased vulnerability of neurones and astrocytes to oxidative damage; furthermore it mediates (in an as yet unknown way) down-regulation of EAAT2 expression. In addition to deficient glutamate clearance, astrocytes may participate in neuronal damage through increased glutamate release: patients with ALS are reported to have increased levels of cyclooxygenase 2, which in turn produces prostaglandin E2; the latter is a potent activator of glutamate release from astrocytes.

How To Reduce Acne Scarring

How To Reduce Acne Scarring

Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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