Brain Neurons Express Ornithine Decarboxylase-Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease
Article first published online: 22 SEP 2009
© 2009 The Authors; Journal Compilation © 2009 International Society of Neuropathology
Volume 20, Issue 3, pages 571–580, May 2010
How to Cite
Mäkitie, L. T., Kanerva, K., Polvikoski, T., Paetau, A. and Andersson, L. C. (2010), Brain Neurons Express Ornithine Decarboxylase-Activating Antizyme Inhibitor 2 with Accumulation in Alzheimer's Disease. Brain Pathology, 20: 571–580. doi: 10.1111/j.1750-3639.2009.00334.x
- Issue published online: 12 APR 2010
- Article first published online: 22 SEP 2009
- Received 10 July 2009; accepted 14 August 2009.
- Alzheimer's disease;
- antizyme inhibitor;
- ornithine decarboxylase;
Polyamines are small cationic molecules that in adult brain are connected to neuronal signaling by regulating inward-rectifier K+-channels and different glutamate receptors. Antizyme inhibitors (AZINs) regulate the cellular uptake of polyamines and activate ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine synthesis. Elevated levels of ODC activity and polyamines are detected in various brain disorders including stroke and Alzheimer's disease (AD).
We originally reported a novel brain- and testis-specific AZIN, called AZIN2, the distribution of which we have now studied in normal and diseased human brain by in situ hybridization and immunohistochemistry. We found the highest accumulation of AZIN2 in a pearl-on-the-string-like distribution along the axons in both the white and gray matter. AZIN2 was also detected in a vesicle-like distribution in the somas of selected cortical pyramidal neurons. Double-immunofluorescence staining revealed co-localization of AZIN2 and N-methyl D-aspartate-type glutamate receptors (NMDARs) in pyramidal neurons of the cortex. Moreover, we found accumulation of AZIN2 in brains affected by AD, but not by other neurodegenerative disorders (CADASIL or Lewy body disease). ODC activity is mostly linked to cell proliferation, whereas its regulation by AZIN2 in post-mitotically differentiated neurons of the brain apparently serves different purposes. The subcellular distribution of AZIN2 suggests a role in vesicular trafficking.