Amyloid beta precursor protein and ubiquitin epitopes in human and experimental dystrophic axons. Ultrastructural localization.

摘要: Dystrophic axons (DA) represent a major pathological feature of several neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and Alzheimer disease. We have previously presented evidence that amyloid beta precursor protein (BPP) ubiquitin (Ub) are present in DA different origin. now characterized the immunoreactivity experimentally induced rat by administration parabromophenylacetylurea (BPAU) examined subcellular localization Ub BPP BPAU-induced subjects affected INAD. strongly immunoreacted with antisera to COOH- NH2-terminal regions BPP. Immunoblots DA-enriched brain were consistent an increase amount DA. Moreover, antibodies PGP 9.5, neuronal-specific COOH-terminal hydrolase, inducible heat shock 70. Antigenic characterization also indicated tubulovesicular membranes within derived largely from smooth endoplasmic reticulum rather than Golgi system or synaptic vesicles. Subcellular immunolocalization both INAD- revealed colocalize granulovesicular material conditions. In INAD intense was detected nonmembranous electron dense structures only these DA, probably because chronic course Although immunostaining may be related accumulation BPP-containing is likely result activation neuron attempt remove excessive possibly abnormal proteins. A similar pathogenesis can postulated for