Fragmentation of the Golgi apparatus in neurodegenerative diseases and cell death.

Fragmentation of the neuronal Golgi apparatus (GA) was reported in amyotrophic lateral sclerosis (ALS), corticobasal degeneration, Alzheimer's and Creutzfeldt-Jacob disease, and in spinocerebelar ataxia type 2 (SCA2). In transgenic mice expressing the G93A mutant of Cu/Zn superoxide dismutase (SOD1) of familial ALS (fALS), fragmentation of the GA of spinal cord motor neurons and aggregation of mutant protein were detected months before the onset of paralysis. Moreover, cells that expressed the G93A and G85R mutants of SOD1 showed fragmentation of the GA and decreased viability without apoptosis.

Dysregulation of stathmin, a microtubule-destabilizing protein, and up-regulation of Hsp25, Hsp27, and the antioxidant peroxiredoxin 6 in a mouse model of familial amyotrophic lateral sclerosis.

Gain-of-function mutations of the Cu/Zn superoxide dismutase (SOD1) gene cause dominantly inherited familial amyotrophic lateral sclerosis. The identification of differentially regulated proteins in spinal cords of paralyzed mice expressing SOD1(G93A) may contribute to understanding mechanisms of toxicity by mutant SOD1. Protein profiling showed dysregulation of Stathmin with a marked decrease of its most acidic and phosphorylated isoform, and up-regulation of heat shock proteins 25 and 27, peroxiredoxin 6, phosphatidylinositol transfer protein-alpha, apolipoprotein E, and ferritin heavy chain.