Melissa Nassif
Assistant Professor
Neurodegenerative diseases are chronic and progressive brain disorders that include Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS). Most cases of these conditions are sporadic, indicating aging as the main risk factor. Unfortunately, currently available pharmacological interventions are limited and mainly focusing on compensating symptoms as opposed to stopping or reversing neuronal loss. These diseases share histopathological features such as accumulation of dysfunctional organelles and misfolded proteins, and dysregulation of autophagic/endocytic pathways. Autophagy is a lysosome-mediated system for the degradation of cytosolic components in which a crescent double-membrane vesicle engulfs the cargo. Mild impairments or dysregulation of autophagic/endocytic homeostatic pathways in neurons have been shown to result in slow, adult-onset neurodegeneration. Our laboratory is dedicated to the understanding of the autophagic and endocytosis processes involved in neurodegeneration and to contribute to the field with potential therapeutic targets for the AD and ALS intervention using complementary approaches (experimental animal models, cell culture).
"My research is dedicated to the understanding of the autophagic and lysosomal processes involved in neurodegeneration and to contribute with new therapeutic targets for intervention in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), using complementary approaches (transgenic animals, culture murine and human cell). We study: 1) the therapeutic potential of proteins that exert their function in the final stages of the autophagic pathway, which we know progressively fail in AD and ALS; in addition 2) we validate the implication of new therapeutic targets found by bioinformatics in the context of AD in human cell cultures (iPS)".
PUBLICATIONS
S. Beltran#, M. Nassif#, E. Vicencio, J. Arcos, L. Labrador, B. I. Cortes, C. Cortez, C. A. Bergmann, S. Espinoza, M. F. Hernandez, J. M. Matamala, L. Bargsted, S. Matus, D. Rojas-Rivera, M. J. M. Bertrand, D. B. Medinas, C. Hetz, P. A. Manque† and U. Woehlbier. 2019. Network approach identifies Pacer as autophagy protein involved in ALS pathogenesis. Molecular Neurodegeneration.
Troncoso-Escudero, P., Parra, A., Nassif, M. Vidal, R.*.2018. Outside in: Unraveling the Role of Neuroinflammation in the Progression of Parkinson’s Disease. Front. Neurol., Suiza, publicada, ISSN 1664-2295, IF: 3.508.
Valenzuela, V., M. Nassif, and C. Hetz. 2018. Unraveling the role of motoneuron autophagy in ALS. Autophagy. doi:10.1080/15548627.2018.1432327.
Nassif, M., U. Woehlbier, and P.A. Manque. 2017. The enigmatic role of C9ORF72 in autophagy. Front. Neurosci. 11. doi:10.3389/fnins.2017.00442.
Nassif, M., V. Valenzuela, D. Rojas-Rivera, R. Vidal, S. Matus, K. Castillo, Y. Fuentealba, G. Kroemer, B. Levine, and C. Hetz. 2014. Pathogenic role of BECN1/Beclin 1 in the development of amyotrophic lateral sclerosis. Autophagy. 10. doi:10.4161/auto.28784.
Nassif, M., D. Medinas, K. Castillo, C. Gherardelli, and C. Hetz. 2014. When the Good Turns Bad: Challenges in the Targeting of Autophagy in Neurodegenerative Diseases. 5.
Matus, S., E. Lopez, V. Valenzuela, M. Nassif, and C. Hetz. 2013. Functional Contribution of the Transcription Factor ATF4 to the Pathogenesis of Amyotrophic Lateral Sclerosis. PLoS One. 8. doi:10.1371/journal.pone.0066672.
Nassif, M., and C. Hetz. 2012. Autophagy impairment: A crossroad between neurodegeneration and tauopathies. BMC Biol. doi:10.1186/1741-7007-10-78.
Nassif, M., and C. Hetz. 2012. Autophagy impairment: A crossroad between neurodegeneration and tauopathies. BMC Biol. 10. doi:10.1186/1741-7007-10-78.
De Vasconcellos-Bittencourt, A.P.S., D.A. Vendite, M. Nassif, L.M. Crema, R. Frozza, A.P. Thomazi, F.B. Nieto, S. Wofchuk, C. Salbego, E.R. Da Rocha, and C. Dalmaz. 2011. Chronic stress and lithium treatments alter hippocampal glutamate uptake and release in the rat and potentiate necrotic cellular death after oxygen and glucose deprivation. Neurochem. Res. 36. doi:10.1007/s11064-011-0404-7.
Nassif, M., and C. Hetz. 2011. Targeting autophagy in ALS: A complex mission. Autophagy. 7. doi:10.4161/auto.7.4.14700.
Nassif, M., S. Matus, K. Castillo, and C. Hetz. 2010. Amyotrophic lateral sclerosis pathogenesis: A journey through the secretory pathway. Antioxidants Redox Signal. 13. doi:10.1089/ars.2009.2991.
Simão, F., L.L. Zamin, R. Frozza, M. Nassif, A.P. Horn, and C.G. Salbego. 2009. Protective profile of oxcarbazepine against oxygen-glucose deprivation in organotypic hippocampal slice culture could involve PI3K cell signaling pathway. Neurol. Res. 31. doi:10.1179/174313209X385671.
Matus, S., M. Nassif, L.H. Glimcher, and C. Hetz. 2009. XBP-1 deficiency in the nervous system reveals a homeostatic switch to activate autophagy. Autophagy. 5. doi:10.4161/auto.5.8.10247.
Galleguillos, D., S. Matus, V. Valenzuela, P. Valdés, A. Martínez, M. Nassif, M. Torres, G. Martínez, and C. Hetz. 2009. Targeting endoplasmic reticulum stress pathways to treat neurological disorders associated with protein misfolding.
Konrath, E.L., K. Santin, M. Nassif, A. Latini, A. Henriques, and C. Salbego. 2008. Antioxidant and pro-oxidant properties of boldine on hippocampal slices exposed to oxygen-glucose deprivation in vitro. Neurotoxicology. 29. doi:10.1016/j.neuro.2008.05.008.
Matus, S., P. Thielen, M. Nassif, M. Torres, and C. Hetz. 2008. Targeting stress pathways to treat neurological disorders linked to protein misfolding.
Nassif, M., J. Hoppe, K. Santin, R. Frozza, L.L. Zamin, F. Simão, A.P. Horn, and C. Salbego. 2007. β-Amyloid peptide toxicity in organotypic hippocampal slice culture involves Akt/PKB, GSK-3β, and PTEN. Neurochem. Int. 50. doi:10.1016/j.neuint.2006.08.008.
Fuentes, P., I. Paris, M. Nassif, P. Caviedes, and J. Segura-Aguilar. 2007. Inhibition of VMAT-2 and DT-diaphorase induce cell death in a substantia nigra-derived cell line - An experimental cell model for dopamine toxicity studies. Chem. Res. Toxicol. 20. doi:10.1021/tx600325u.
Cimarosti, H., R.D. O’Shea, N.M. Jones, A.P. Horn, F. Simão, L.L. Zamin, M. Nassif, R. Frozza, C.A. Netto, P.M. Beart, and C. Salbego. 2006. The effects of estradiol on estrogen receptor and glutamate transporter expression in organotypic hippocampal cultures exposed to oxygen-glucose deprivation. Neurochem. Res. 31. doi:10.1007/s11064-006-9043-9.
Zamin, L.L., P. Dillenburg-Pilla, R. Argenta-Comiran, A.P. Horn, F. Simão, M. Nassif, D. Gerhardt, R.L. Frozza, and C. Salbego. 2006. Protective effect of resveratrol against oxygen-glucose deprivation in organotypic hippocampal slice cultures: Involvement of PI3-K pathway. Neurobiol. Dis. 24. doi:10.1016/j.nbd.2006.06.002.
Cimarosti, H., I.R. Siqueira, L.L. Zamin, M. Nassif, R. Balk, R. Frozza, C. Dalmaz, C.A. Netto, and C. Salbego. 2005. Neuroprotection and protein damage prevention by estradiol replacement in rat hippocampal slices exposed to oxygen-glucose deprivation. Neurochem. Res. 30. doi:10.1007/s11064-005-2693-1.
Cimarosti, H., L.L. Zamin, R. Frozza, M. Nassif, A.P. Horn, A. Tavares, C.A. Netto, and C. Salbego. 2005. Estradiol protects against oxygen and glucose deprivation in rat hippocampal organotypic cultures and activates Akt and Inactivates GSK-3β. Neurochem. Res. 30. doi:10.1007/s11064-004-2441-y.
RESEARCH LINES
"My research is dedicated to the understanding of the autophagic and lysosomal processes involved in neurodegeneration and to contribute with new therapeutic targets for intervention in Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), using complementary approaches (transgenic animals, culture murine and human cell). We study: 1) the therapeutic potential of proteins that exert their function in the final stages of the autophagic pathway, which we know progressively fail in AD and ALS; in addition 2) we validate the implication of new therapeutic targets found by bioinformatics in the context of AD in human cell cultures (iPS)".
PROJECTS
Name: FONDECYT Iniciación
Title: Involvement of Rubicon-Like Family Members in Neurodegeneration and Their Potential as Therapeutic Targets.
Sponsor Institution: FONDECYT
Date of Execution: 2016-2019
Name: FONDECYT Regular
Title: RCAN1 trisomy and the control of PINK1 levels in the survival of human Down's syndrome induced pluripotent stem cells (iPSC).
Sponsor Institution FONDECYT
Date of Execution: 2019-2023
TEAM
Wileidy Gomez
PhD student in Integrative Genomics
She works with the search for new genes whose expression is shared between Alzheimer's disease and Down Syndrome by bioinformatics and then will validate it in iPS cell and neurons derived from iPS of individuals of both pathologies.
José Matías Benitez
Undergraduate student in Biotechnology
he studies the role of a poorly characterized protein in the developing nervous system in a zebra fish model.
Sandra Espinoza
Assistan Research
Responsible for carrying out studies in murine genetic models of ALS and AD. Sandra is also the lab manager.
NETWORK
National
Ute Woehbier, Universidad Mayor, Centro de Biología Integrativa
Rene Vidal, Universidad Mayor, Centro de Biología Integrativa
Carol San Martin, Universidad Mayor, Centro de Biología Integrativa
Leonardo Valdivia, Centro de Biología Integrativa
Mario Sanhueza, Centro de Biología Integrativa
Claudio Hetz, Universidad de Chile
Valentina Parra, Universidad de Chile
María Isabel Behrens, M.D. Universidad de Chile
Vinicius Coutinho, Universidad de Chile
Fernando Ezquer, Universidad del Desarrollo