Syndromic Autism?
Two patients have been found in Córdoba capital with the same DLAT 1541 C>T mutation, in heterozygosity, curiously not described in the scientific literature. These patients present multiple symptoms associated with mitochondrial dysfunction, such as: dystonia, general lethargy, gastrointestinal disorders and autism spectrum symptoms. We propose to study the effect of this point mutation on mitochondrial activity, energy metabolism and cell viability.
Cellular aging in Down syndrome
Considering our published observations, we propose that there is a mechanistic relationship between accelerated cellular senescence in Down Syndrome and mitochondrial dysfunction associated with oxidative damage. We are evaluating common pathways that are observed in other human autosomal trisomies, and the activation of antioxidant cellular responses as a palliative to the phenomenon.
COMPETITIVE RESEARCH FUNDS
- 2021- 2024. PICT 2019-00306. El rol del Desbalance Cromosómico en el proceso de Envejecimiento. Director.
- 2017- 2020. PIP 2015-2017 – CONICET. Mecanismo molecular involucrado en El incremento de la producción del péptido amiloide beta inducida por la deposición de ab:Mecanismo patogénico de Retroalimentación positiva en la enfermedad de alzheimer.Cotitular
- 2014-2017. PICT 2013-3142. El rol del Desbalance Cromosómico en el proceso de envejecimiento. Director.
- 2013-2014 Proyecto de investigación y desarrollo tecnológico E-Perspective S.A.-INIMEC-CONICET-UNC. Estudio para determinar la factibilidad de la utilización del “Self Adhesive Security Sticker®” y el kit “Fingerprint DNA finder” para diagnóstico genético. Investigador responsable técnico.
- 2011-2013. PIP 2011-2013 – CONICET. Participación de la proteína Precursora de Amiloide β (APP) en la neurodegeneración inducida por Amiloide β: Relevancia para la enfermedad de Alzheimer. Cotitular.
- 2007-2010. FEL. Hillblom Fdn Inc. Fellowship. University of California-Irvine. «Molecular Mechanisms Associated with Type 2 Diabetes in Down’s Syndrome».
PUBLICATIONS (LATEST FIVE YEARS)
- Dierssen M., Herault Y., Helguera P., et al. Building the Future Therapies for Down Syndrome: The Third International Conference of the T21 Research Society. Mol Syndromol 2021;12:202–218 Mol Syndromol doi:10.1159/000514437
- Hwang S, Williams JF, Kneissig M, Lioudyno M, Rivera I, Helguera P, Busciglio J, Storchova Z, King MC, Torres EM. 2019. Suppressing Aneuploidy-Associated Phenotypes Improves the Fitness of Trisomy 21 Cells. Cell Rep. 2019;29(8):2473‐2488.e5. doi:10.1016/j.celrep.2019.10.059
- Zamponi E, Helguera P. 2019. The Shape of Mitochondrial Dysfunction in Down Syndrome. Dev Neurobiol. Jul;79(7):613-621. doi: 10.1002/dneu.22673. Epub 2019 Mar 13.
- Zamponi E, Zamponi N, Coskun P, Quassollo G, Lorenzo A, Cannas S, Pigino, Gustavo; Chialvo, D, Gardiner K, Busciglio J, Helguera P. 2018. Nrf2 stabilization prevents critical oxidative damage in Down syndrome cells. Aging Cell. 17(5): e12812.
- Zamponi N, Zamponi E, Cannas S, Billoni O, Helguera P, Chialvo, D. 2018. Mitochondrial network complexity emerges from fission/fusion dynamics. Scientific Reports. 2018; 8: 363.
- Zamponi E, Buratti F, Cataldi G, Caicedo H, Song Y, Jungbauer L, Ladu M, Bisbal M, Lorenzo A, Ma J, Helguera P, Morfini G, Brady S, Pigino G. 2017. Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2. PLOS ONE. 2017 Dec 20;12(12):e0188340.
- Coskun P, Helguera P, Nemati Z, Bohannan RC, Thomas J, Samuel SE, Argueta J, Doran E, Wallace DC, Lott IT, Busciglio J. 2016. Metabolic and Growth Rate Alterations in Lymphoblastic Cell Lines Discriminate Between Down Syndrome and Alzheimer’s Disease. J Alzheimers Dis. Nov 19;55(2):737-748.
- Helguera P, Seiglie J, Rodriguez J, Hanna M, Helguera G and Busciglio J. 2013. Adaptive downregulation of mitochondrial function in Down’s syndrome. Cell Metabolism, 17:132–140
- Complete and updated list available here.
TEAM
