El envejecimiento está asociado a un aumento en la incidencia de enfermedades neurodegenerativas y la patología parkinsoniana, degeneración dopaminérgica (DA) nigro-estriatal,es un fiel reflejo de la vulnerabilidad de las neuronas DA asociada a la edad; con un mecanismo molecular responsable del proceso degenerativo aún desconocido. En la EP, por el complejo circuito motor que involucra no solo a los ganglios de la base el deterioro cognitivo adquiere un rol relevante, precediendo a los síntomas motores al momento del diagnóstico y culminando en la mayoría de los casos, en demencia al progresar la enfermedad. El empleo de vectores adenovirales portadores de factores neurotróficos y de terapias antiinflamatorias optimizadas para prevenir la neurodegeneración, aumentar la capacidad de recuperación, plasticidad sináptica y por lo tanto funcionalidad de circuitos hipocampales vinculados a memoria y aprendizaje, emergen como abordajes terapéuticos promisorios.
El objetivo general actual de las investigaciones que llevamos a cabo es realizar abordajes neurobiológicos y terapéuticos tempranos que ayuden a comprender y mejorar procesos inflamatorios y plásticos sinápticos asociados al declinamiento cognitivo y motor en el modelo parkinsoniano de neurodegeneración nigro-estriatal con 6-OH Dopamina y al envejecimiento natural.

Macarena Lorena Herrera, Leandro Gabriel Champarini, Osvaldo Martín Basmadjian, María José Bellini and Claudia Beatriz Hereñú. IGF-1 gene therapy prevents spatial memory deficits and modulates dopaminergic neurodegeneration and inflammation in a parkinsonism model. Brain Behav Immun. 2024 Jul;119:851-866. doi: 10.1016/j.bbi.2024.05.013. Epub 2024 May 16.PMID: 38750702

Priscila Chiavellini, Marianne Lehmann, Maria D. Gallardo, Martina Canatelli Mallat, Diana C. Pasquini, Joseph A. Zoller, Juozas Gordevicius, Mauricio Girard, Ezequiel Lacunza, Claudia B. Herenu, Steve Horvath, Rodolfo G. Goya. Young plasma rejuvenates blood DNA methylation profile, extends mean lifespan and improves physical appearance in old rats. Journal of Gerontology: Biological Sciences-JGBS J Gerontol A Biol Sci Med Sci. 2024 May 1;79(5): glae071. doi: 10.1093/gerona/glae071. PMID: 38430547.

Claudia Hereñú and Rosana Crespo. Phytochemicals as estrogen receptor modulators?- a commentary of a network pharmacology study of two commonly employed Chinese herbal medicines in the treatment of non-small cell lung cancer. Transl Cancer Res. 2023 Dec 31;12(12):3249-3254. doi: 10.21037/tcr-23-1440. Epub 2023 Nov 27.PMID: 38197069

Champarini L, Herrera ML, Comas Mutis RG, Espejo PJ, Molina VA, Calfa GD*, Hereñú CB*. *Equal contribution Effect of intra-BLA overexpression of IGF-1 on the expression of a contextual fear memory trace Hippocampus. 2022 Oct;32(10):765-775. doi: 10.1002/hipo.23465. Epub 2022 Aug 24.PMID: 36000813 Impact factor: 3,25

Chiavellini P, Lehmann M, Canatelli Mallat M, Zoller JA, Herenu CB, Morel GR, Horvath S, Goya RG . Hippocampal DNA Methylation, Epigenetic Age and Spatial Memory Performance in Young and Old Rats. J Gerontol A Biol Sci Med Sci. 2022 Dec 29;77(12):2387-2394. doi: 10.1093/gerona/glac153.PMID: 35917578

Eugenia Falomir-Lockhart, Franco Dolcetti, Macarena Herrera, Jerónimo Pennini, María Florencia Zappa Villar, Gabriela Salinas, Enrique Portiansky, Björn Spittau, Ezequiel Lacunza, Claudia B. Hereñú*, Maria Jose Bellini 1*. * Equal contribution. IGF-1 gene transfer modifies microglia phenotype and gene expression in the Caudate-Putamen of female aged rat brain – Mol Neurobiol. 2022 Mar 19. doi: 10.1007/s12035-022-02791-

Herrera, Macarena L.; Bandín, Sandra; Champarini, Leandro G.; Hereñú, Claudia B.; Bellini, Maria Jose. Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury. BRAIN RESEARCH BULLETIN. 2021; 175 p. 196 – 204. doi.org/10.1016/j.brainresbull.2021.07.023

Chiavellini P, Canatelli-Mallat M, Lehmann M, Gallardo MD, Herenu CB, Cordeiro JL, Clement J, Goya RG. Aging and rejuvenation – a modular epigenome model. Aging (Albany NY). 2021 ;13(4):4734-4746. doi: 10.18632/aging.202712. Epub 2021 Feb 24.PMID: 33627519

Montivero AJ, Ghersi MS, Silvero C MJ, Artur de la Villarmois E, Catalan-Figueroa J, Herrera M, Becerra MC, Hereñú CB, Pérez MF. Early IGF-1 Gene Therapy Prevented Oxidative Stress and Cognitive Deficits Induced by Traumatic Brain Injury. Front Pharmacol. 2021;12:672392. doi: 10.3389/fphar.2021.672392. eCollection 2021.PMID: 34234671

Herrera M., Basmadjian OM., Falomir Lockhart E., Dolcetti FJC., Hereñú CB.*, Bellini MJ.* Sex-frailty differences in aging mice: neuropathologies and therapeutic projections. Eur J Neurosci. 2020.Bioxbio Journal IF 3,115. doi: 10.1111/ejn.14703.

Fabián Nishida, Carolina N. Zanuzzi , María S. Sisti , Eugenia Falomir Lockhart , Agustina E. Camiña, Claudia B. Hereñú, María J. Bellini, Enrique L. Portiansky . Intracisternal IGF-1 gene therapy abrogates kainic acid-induced excitotoxic damage of the rat spinal cord. Eur J Neurosci. 2020 Sep;52(5):3339-3352. doi: 10.1111/ejn.14876.

Herrera M.L.a, Ghersi M.S.a, Artur de la Villarmois E.a, Deza-Ponzio R.a, Virgolini M a, Pérez MF.a, Molina VA.a, Bellini MJ.b* and Hereñú CB.a*. * These two authors contributed equally to this work a(IFEC-CONICET-UNC) b(INIBIOLP-CONICET-UNLP). Corresponding authors: Hereñú C. and Bellini MJ. Early cognitive impairment behind nigro-striatal circuit neurotoxicity: are astrocytes involved? ASN Neuro mayo 2020. Doi: 10.1177/1759091420925977

Herrera M., Basmadjian OM., Falomir Lockhart E., Dolcetti FJC., Hereñú CB.*, Bellini MJ.*.* These two authors contributed equally to this work. Novel adenoviral IGF-I administration modulates the association between depressive symptoms and aging: Does gender matter?”. Corresponding authors: Hereñú C. and Bellini MJ. Behavioural Brain Research . 2019 Jun 20;372:112050. doi: 10.1016/j.bbr.2019.112050.

Falomir-Lockhart E, Dolcetti FJC, García-Segura LM, Hereñú CB*, Bellini MJ*. *These two authors contributed equally to this work. IGF1 Gene Therapy Modifies Microglia in the Striatum of Senile Rats.Corresponding authors: Hereñú C. and Bellini MJ. Front Aging Neurosci. 2019 Mar 5; 11:48. doi: 10.3389/fnagi.2019.00048. eCollection 2019

Lehmann M, Canatelli-Mallat M, Chiavellini P, Morel GR, Reggiani PC, Hereñú CB, Goya RG. Regulatable adenovector harboring the GFP and Yamanaka genes for implementing regenerative medicine in the brain.Gene Ther. 2019 Feb 15. doi: 10.1038/s41434-019-0063-x

Herrera Macarena Lorena, Champarini Leandro Gabriel, Otamendi Andrea, Hereñú Claudia Beatriz. Fearing Parkinson’s disease: relationships between cognition and emotion. (Book Chapter) Psychiatry and Neuroscience Update. 4th Edition © Springer International Publishing Switzerland – ISBN 978-3-319-17102-9 (eBook) 2018- Editores: Gargiulo, Pascual Angel, Mesones Arroyo, Humberto Luis (Eds.) (2018). 4th Edition. ISBN 978-3-319-95360-1 (Book Chapter)

Romina Deza-Ponzioa*, Macarena L. Herreraa,b*, María J.Bellinib, Miriam B. Virgolinia and Claudia B. Hereñúa. Corresponding author: Hereñú C. Aldehyde Dehydrogenase 2 in the spotlight: the link between mitochondria and neurodegeneration. Neurotoxicology. 2018 Jun 21; 68:19-24.

Pereyra AS, Mykhaylyk O, Lockhart EF, Taylor JR, Delbono O, Goya RG, Plank C, Hereñu CB. Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells. J Nanomed Nanotechnol. 2016 Apr;7(2). pii: 364. Epub 2016 Apr 5.

Morel GR, Andersen T, Pardo J, Zuccolilli GO, Cambiaggi V, Hereñú CB*, Goya RG*; * These two authors contributed equally to this work. Cognitive impairment and morphological changes in the dorsal hippocampus of very old female rats; Neuroscience 2015, Jun 30; 303:189-199.

Hereñú CB, Sonntag WE, Morel GR, Portiansky EL, Goya RG. The ependymal route for insulin-like growth factor-1 gene therapy in the brain. Neuroscience (2009) Sep 29;163(1):442-7.