Neuronal Thread Protein Gene Modulation With Cerebral Infarction

Neuronal thread proteins (NTP) are a family of phosphoproteins expressed during neuritic sprouting. The 15 to 18 kD NTP cluster is associated with development and neuronal differentiation, whereas the 21 kD and 39 to 42 kD species are overexpressed in Alzheimer's disease, correlating with neurodegenerative sprouting and synaptic disconnection. Empirical observations suggested that NTP might also be modulated with central nervous system injury and stroke. In this study of both human and experimental (rat) focal cerebral infarcts, in situ hybridization and immunocytochemical staining revealed NTP gene expression up-regulated in perifocal neurons. These findings were confirmed by quantitative Northern and Western blot analyses. Moreover, Western blot analysis demonstrated selectively increased expression of the 15 to 18 kD NTP species during the acute, subacute, and healing phases of cerebral infarction in both humans and experimental animals, corresponding with the expected period of neuronal repair. These results suggest an additional role for the 15 to 18 kD NTP species in neuritic sprouting required for neuronal regeneration after injury in the mature central nervous system.

New Biochemical Insights to Unravel the Pathogenesis of Alzheimer's Lesions

ABSTRACT:Purification of amyloid plaque core proteins (APCP) from Alzheimer's disease brains to complete homogeneity and in high yield permitted its chemical fractionation and characterization of its components. APCP is mainly made of β-amyloid (βA) and an assortment of glycoproteins (accounting for 20%) rich in carbohydrates compatible with N-and O-linked saccharides. When added to tissue culture of sympathetic and sensory neurons APCP and βA inhibited neuritic sprouting, a reversible phenomenon at low doses. Higher concentrations of both substances kill the neurons in culture. APCP is significantly more toxic than βA, suggesting the minor components may play an important role in increasing the toxicity of βA. If the observed toxic effects of APCP in situ are occurring in vivo during the course of AD, then the accumulation of these extracellular proteins could be largely responsible for some of the neuronal death observed in this neuropathology.