Huntington’s Disease (HD) is a neurodegenerative disorder for which no treatment has been identified to prevent, limit, or cure symptoms of involuntary choreiform movements, behavioral abnormalities, dementia, and motor dysfunction as a result of neuronal loss in the striatum and cerebral cortex. Although it is known that HD is caused by mutations in the huntingtin gene, the causality of this mutation in the mechanism of neuronal loss remains unknown. Compelling evidence suggests that increased oxidative stress and mitochondrial dysfunction contribute to the pathophysiology of HD, thus, a better understanding of why mitochondrial dysfunction may arise during HD neurodegeneration could provide the basis for the development of new pharmacological interventions to delay disease onset and progression. Our experimental plan is based on testing a hypothesis that targets the main endonuclease, APE1, associated with repair of mitochondrial DNA (mtDNA) against oxidative stress as a potential target to prevent HD. To test our hypothesis, we apply cellular, biochemical and molecular approaches using both in vitro and in vivo experimental models. We also test small molecules with antioxidant activity as interventions to prevent onset and/or progression of the disease. Because aging is the main risk factor for chronic diseases and is associated with increased DNA damage and decreased DNA repair capacity, we are also studying the role of mitochondria in diabetes, an age-associated disorder, and testing pharmacological interventions that may protect mtDNA integrity and mitochondrial function.

2021:

• Nadalutti CA, Ayala-Peña S, Santos JH. Mitochondrial DNA damage as driver of cellular outcomes. Am J Physiol Cell Physiol. 2021 Dec 22. doi: 10.1152/ajpcell.00389.2021. Epub ahead of print. PMID: 34936503.

2020:

• Lozada-Delgado, J, Torres-Ramos, C, and Ayala-Peña, S. (2020). Aging, oxidative stress, mitochondrial dysfunction and the liver. 10.1016/B978-0-12-818698-5.00004-3.

2019:

• Parodi-Rullán R, Chapa-Dubocq X, Guzmán-Hernández R, Jang S, A Torres-Ramos C, Ayala-Peña S, Javadov S. The role of adenine nucleotide translocase in the assembly of respiratory supercomplexes in cardiac cells. Cells. 2019 Oct 13;8(10). pii: E1247. doi: 10.3390/cells8101247.

2018:

• Preston AM, Rodríguez-Orengo J, González-Sepúlveda L, Ayala-Peña S, Maldonado-Maldonado E. Effect of Housing Type on 25 OH Vitamin D in Serum of Rhesus Monkeys. PR Health Sci J. 2018 Jun;37(2):124-127. PMID: 29905924

2017:

• Ballista-Hernandez J, Martinez-Ferrer M, Velez R, Climent C, Sanchez-Vazquez MM, Torres C, Rodriguez-Munoz A, Ayala-Peña S, Torres-Ramos CA. Mitochondrial DNA Integrity is Maintained by APE1 in Carcinogen-induced Colorectal Cancer. Mol Cancer Res.2017 Mar 30. pii: molcanres.0218.2016. doi: 10.1158/1541-7786.MCR-16-0218. PMID: 28360037
• De Mello WC, Gerena Y and Ayala-Peña S. Angiotensins and Huntington’s disease: A study on Immortalized Progenitor Striatal Cell Lines. Frontiers in Endocrinology May 2017 doi: 10.3389/fendo.2017.00108

 

2016:

• Polyzos A, Holt A, Brown C, Cosme C Wipf P, Gomez Marin A, Castro MR, Ayala-Peña S and McMurray CT. Mitochondrial targeting of XJB-5-131 attenuates or improves pathophysiology in HdhQ150 animals with well-developed disease phenotypes. Hum Mol Genet Feb 21 (2016) PMID: 26908614
• Padín-Irizarry V, Colón-Lorenzo EE, Vega-Rodríguez J, Castro MD, González-Méndez R, Ayala-Peña S and Serrano, AE. Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage. Free Rad Biol Med Mar 4 (2016) PMID: 26952808

 

2015:

• Budworth H, Harris FR, Williams P, Lee DY, Holt A, Pahnke J, Szczesny B, Acevedo-Torres K, Ayala-Peña S and McMurray CT. Suppression of somatic expansion delays the onset of pathophysiology in a mouse model of Huntington’s disease. PLOS Genetics. 11(8):e10005267 2015. doi:10.1371. PMID: 26247199

2014:

• Ayala-Peña, S and Torres-Ramos, CA. Oxidative stress contributes to liver pathology during aging. In: Oxidative Stress and Dietary Antioxidants. Edited by Prof. Victor R. Preedy. Elsevier. 2014.
• Rivera-Sánchez S, McMurray CT, and Ayala-Peña, S. Mitochondrial dysfunction in brain and muscle pathology of Huntington’s disease. In: Systems Biology of Free Radicals and Antioxidants. Edited by I. Laher. Springer-Verlag. 2014
• López-López L, Nieves-Plaza M, Castro M del R, Font I, Torres-Ramos CA, Vilá-Perez L and Ayala-Peña, S. Mitochondrial DNA damage is associated with damage accrual and disease duration in patients with Systemic Lupus Erythematosus. Lupus, June 4, 2014 PMID: 24899636
• Jansen RJ, Fonseca-Williams S, Bamlet WR, Ayala-Peña S, Oberg AL, Petersen GL and Torres-Ramos CA. Detection of DNA Damage in Peripheral Blood Mononuclear Cells from Pancreatic Cancer Patients. Molecular Carcinogenesis. 2014 Aug 11. Doi: 10.1002/mc.22189. PMID: 25111947
• Escobales N, Nuñez RE, Jang S, Parodi-Rullan R, Ayala-Peña S, Sacher JR, Skoda EM, Wipf P, Frontera W, Javadov S. Mitochondria-targeted ROS scavenger improves post-ischemic recovery of cardiac function and attenuates mitochondrial abnormalities in aged rats. J Mol Cell Cardiol. 2014 Dec;77:136-46. doi: 10.1016/j.yjmcc.2014.10.009. PMID: 25451170

2013:

• Ayala-Peña, S. Role of Oxidative DNA Damage in Mitochondrial Dysfunction and Huntington’s Disease Pathogenesis. Free Rad Biol and Med 62:102–110. 2013.

2012:

• Almas Siddiqui, Sulay Rivera-Sánchez, María del R. Castro, Karina Acevedo-Torres, Anand Rane, Carlos A. Torres-Ramos, David G. Nicholls, Julie K. Andersen and Sylvette Ayala-Torres. 2012. Mitochondrial DNA damage is associated with reduced mitochondrial bioenergetics in Huntington’s disease. Free Radical Biology and Medicine Oct 1. 53 (2012) 1478–1488. PMID: 22709585
• Xun, Z, Sulay Rivera-Sanchez, Ayala-Peña, S, Lim, J, Budworth, H, Skoda, EM, Robbins, PD, Niedernhofer, LJ, Wipf, P and McMurray, CT. Targeting of XJB-5-131 to Mitochondria Suppresses Oxidative DNA Damage and Motor Decline in a Mouse Model of Huntington’s Disease. Cell Reports 2012, Oct 30. PMID: 23122961
• Castro, María del R., Suarez, Edu, Kraiselburd, Edmundo, Isidro, Angel, Paz, José, Ferder, León and Ayala-Torres, Sylvette. 2012. Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys. Experimental Gerontology 47:29-37.

2011:

• Kristine S. Vogel, Marissa Perez, Jamila R. Momand, Karina Acevedo-Torres, Kim Hildreth, Rebecca A. Garcia, Carlos A. Torres-Ramos, Sylvette Ayala-Torres, Thomas J. Prihoda, C. Alex McMahan, and Christi A. Walter. 2011. Age-Related Instability in Spermatogenic Cell Nuclear and Mitochondrial DNA Obtained from Apex1 Heterozygous Mice. Molecular Reproduction and Development 8(12): 906-19.

2009:

• Acevedo-Torres, Berríos, L., Rosario, N., Dufault, V., Skatchkov, S., Eaton, M.J., Torres-Ramos, C.A., and Ayala-Torres, S. 2009. Mitochondrial DNA damage is a hallmark of chemically-induced and the R6/2 transgenic model of Huntington’s disease. DNA Repair 8:126-136.
• Acevedo-Torres, K., Fonseca, S., Ayala-Torres, S., and Torres-Ramos, C.A. 2009. Requirement of the Saccharomyces cerevisiae APN1 Gene for the Repair of Alkylation and Oxidative Mitochondrial DNA Damage. Environmental & Molecular Mutagenesis 50:317-327.

2000:

• Ayala-Torres, S., Chen, Y., Svoboda, T., Rosenblatt, J., and Van Houten, B. 2000. Analysis of gene-specific DNA damage and repair using quantitative polymerase chain reaction. In Methods: A Companion to Methods in Enzymology. Doetsch, P. W., Issue Ed., Academic Press, NY. 22, 135-147.

 

Additional Publications:

• Ayala-Torres, S. and Thompson, E. B. 2002. Oxysterol-Induced Apoptosis in Lymphoid Cells. In: Sterols and Oxysterols: Chemistry, Biology, and Pathobiology. Steven J. Fliesler, Volume Editor; Research Signpost, Trivandrum-695 008, India. 159-173.
• Johnson, B.H., Rusell, M. J., Krylov, A.S., Medh, R.D., Ayala-Torres, S., Regner, J.L., and Thompson, E.B. 2000. Structure-apoptotic potency evaluations of novel sterols using human leukemic cells. Lipids 35, 305-315.
• Ayala-Torres, S., Zhou, F., and Thompson, E.B. 1999. Apoptosis Induced by Oxysterol in CEM Cells is Associated with Negative Regulation of c-Myc. Exp. Cell Res. 246, 193-202.
• Thompson, E.B., Medh, R.D., Zhou,, F., Ayala-Torres, S., Ansari, N., Zhang, W., and Johnson, B.H. 1999. Glucocorticoids, oxysterols, and cAMP with glucocorticoids each cause apoptosis of CEM cells and suppress c-myc. J. Steroid Biochem. Molec. Biol. 69, 453-461.
• Hodgson, A. V., Ayala-Torres, S., Thompson, E. B., and Liehr, J. G. 1998. Estrogen-induced microsatellite DNA alterations are associated with Syrian hamster kidney tumorigenesis. Carcinogenesis, 19, 2169-2172.
• Ayala-Torres, S., Moller, P. C., Johnson, B.H., and Thompson, E.B. 1997. Characteristics of 25-hydroxycholesterol-induced apoptosis in the human leukemic cell line CEM. Exp. Cell Res., 235, 35-47.
• Johnson, B.H., Ayala-Torres, S., Chan, L.-N.L., El-Naghy, M., and Thompson, E.B. 1997. Glucocorticoid/oxysterol-induced DNA lysis in human leukemic cells. J. Steroid Biochem. Molec. Biol., 61, 35-45.
• Ayala-Torres, S., Johnson, B. H., and Thompson, E. B. 1994. Oxysterol sensitive and resistant lymphoid cells: correlation with regulation of cellular nucleic acid binding protein mRNA. J. Steroid Biochem. Molec. Biol. 48:307-315.
• Thompson, E. B. and Ayala-Torres, S. 1999. Oxysterols and apoptosis: evidence for gene regulation outside the cholesterol pathway. Crit. Rev. Biochem. Mol. Biol. 34, 25-32.