Ivan Yurov

Svetlana Vorsanova

Thomas Liehr

Yuri Yurov

Molecular Neurodegeneration

PubMed

Springer - Publisher Connector

POSTER PRESENTATION Open Access
Ataxia-telangiectasia paradoxes: spotlight on
post-zygotic chromosome instability in the brain
and its contribution to neurodegeneration
pathways
Yuri Yurov1,3*, Svetlana Vorsanova2,3, Thomas Liehr4, Ivan Yurov1,5
From Molecular Neurodegeneration: Basic biology and disease pathways
Cannes, France. 10-12 September 2013
Background
Ataxia-telangiectasia is a syndrome of chromosome
instability (CIN) featured by progressive neurodegenera-
tion affecting the cerebellumin in contrast to other brain
areas. Previously, progressive neuronal death in AT was
hypothesized to be driven by increased post-zygotic CIN
in the cerebellum [1-3]. To assess the possible involvement
of neural CIN in neurodegenerative pathways we have
analyzed CIN in AT brain.
Materials and methods
CIN was evaluated by high-resolution single cell
(immuno-) FISH techniques in 7 AT and 7 control
samples. Bioinformatics analyses of neurodegeneration
pathways were done as described earlier [4].
Results
Global aneuploidization affecting 20% of neurons and 80%
of glial cells in the prefrontal cortex and cerebellum was
observed. CIN in the cerebellum has affected specific
chromosomes (7, 14, and X) similarly the immune system.
Paradoxically, dramatic and age-dependent increase in the
pathological level of CIN did not result in accelerated
neurodegeneration in the brain of patients, but was
associated with increased lifespan. Bioinformatics analyses
have shown that the SMAD pathway is implicated in
neurodegeneration in addition to genome integrity
maintenance, somatic V(D)J recombination and DNA
damage response in neural cells.
Conclusions
To explain paradoxes we hypothesized that progressive
neurodegeneration in the cerebellum can be associated
with activation of adult neurogenesis in the diseased cere-
bellum and/or activation and proliferation of microglia -
the phagocyte system of the brain. Neurodegeneration
pathways in the AT brain are likely to be applicable to
disorders exhibiting neurogeneration in specific brain
areas.
Acknowledgements
Supported by BMBF/DLR (BLR 11/002), the Russian Federation President
Grant (MD-4401.2013.7), RFBR 12-04-00215-a.
Authors’ details
1Mental Health Research Center, Russian Academy of Medical Sciences,
Moscow, Russia. 2Institute of Paediatrics and Paediatric Surgery, Ministry of
Health, Moscow, Russia. 3Moscow City University of Psychology and
Education, Moscow, Russia. 4Institute of Human Genetics, Jena, Germany.
5Department of Medical Genetics, Russian Medical Academy of Postgraduate
Education, Moscow, Russia.
Published: 13 September 2013
References
1. lourov IY, Vorsanova SG, Liehr T, Yurov YB: Aneuploidy in the normal,
Alzheimer’s disease and ataxia-telangiectasia brain: differential
expression and pathological meaning. Neurobiol Dis 2009, 34:212-220.
2. lourov IY, Vorsanova SG, Liehr T, Kolotii AD, Yurov YB: Increased
chromosome instability dramatically disrupts neural genome integrity
and mediates cerebellar degeneration in the ataxia-telangiectasia brain.
Hum Mol Genet 2009, 18:2656-2669.
3. Yurov YB, Vorsanova SG, Tagirova MK, lourov IY: Genetic paradoxes of
neurodegeneration in ataxia telangiectasia (Louis-Bar syndrome).
Fundamental research 2013, 1(part 2):315-326.
4. lourov IY, Vorsanova SG, Kurinnaia OS, Zelenova MA, Silvanovich AP,
Yurov YB: Molecular karyotyping by array CGH in a Russian cohort of
1Mental Health Research Center, Russian Academy of Medical Sciences,
Moscow, Russia
Full list of author information is available at the end of the article
Yurov et al. Molecular Neurodegeneration 2013, 8(Suppl 1):P51
http://www.molecularneurodegeneration.com/content/8/S1/P51
© 2013 Yurov et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons
Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in
any medium, provided the original work is properly cited.
children with intellectual disability, autism, epilepsy and congenital
anomalies. Mol Cytogenet 2012, 5:46.
doi:10.1186/1750-1326-8-S1-P51
Cite this article as: Yurov et al.: Ataxia-telangiectasia paradoxes:
spotlight on post-zygotic chromosome instability in the brain and its
contribution to neurodegeneration pathways. Molecular
Neurodegeneration 2013 8(Suppl 1):P51.
Submit your next manuscript to BioMed Central
and take full advantage of: 
• Convenient online submission
• Thorough peer review
• No space constraints or color figure charges
• Immediate publication on acceptance
• Inclusion in PubMed, CAS, Scopus and Google Scholar
• Research which is freely available for redistribution
Submit your manuscript at 
www.biomedcentral.com/submit
Yurov et al. Molecular Neurodegeneration 2013, 8(Suppl 1):P51
http://www.molecularneurodegeneration.com/content/8/S1/P51
Page 2 of 2


Ataxia-telangiectasia paradoxes: spotlight on post-zygotic chromosome instability in the brain and its contribution to neurodegeneration pathways

http://dx.doi.org/10.1186/1750-1326-8-S1-P51

Ataxia-telangiectasia paradoxes: spotlight on post-zygotic chromosome instability in the brain and its contribution to neurodegeneration pathways

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector