Alzheimer´s disease (AD) is the main cause of cognitive impairment and dementia in elderly people. AD is a progressive neurodegenerative pathology with no effective treatment with an increasing incidence worldwide. Therefore, AD represents a major global medical, social, and economic burden. AD is characterized by cerebral accumulation of Amyloid beta (Aβ) and neuronal degeneration in brain areas involved in superior cognitive functions (Figure 1). Aβ is a 40-42 amino acid peptide derived from metabolic processing of Amyloid precursor protein (APP). The dominant hypothesis posit that Aβ accumulation triggers neuronal degeneration and cognitive impairment in AD. However, the mechanism of Aβ neurotoxicity remains elusive and is the focus of intense research and scientific controversy. Dr Lorenzo´s research aims to expand the knowledge of the mechanism of Aβ toxicity, and particularly to elucidate the role of APP and Go protein signaling. His is using cellular and molecular approaches, including biosensors for studying APP-Go interaction (Figure 2) and human neuronal cultures generated form isogenic pluripotent stem cells cellular with for studying APP mutations related to Go signaling (Figures 3).
COMPETITIVE RESEARCH FUNDS
- 2019-2023 ANPCyT PICT2018-02097. Diseño de herramientas moleculares terapéuticas para la enfermedad de Alzheimer. PI
- 2022-2025 Grant from Alzheimer’s Association Research Grant to Promote Diversity (AARGD-22-926476). “Strategies disrupting the feed-forward mechanism of Aß production”. PI. Dra Elena A Bignante – Co-Pi: Alfredo Lorenzo
PUBLICATIONS (LATEST FIVE YEARS)
- de Olmos S and Lorenzo A. Developing the theory of the extended amygdala with the use of the cupric-silver technique. Journal of the History of the Neurosciences (NJHN)- DOI: 10.1080/0964704X.2022.2133569
- Antonino M, Marmo P, Freites CL, Quassollo G, Sanchez MF, Lorenzo A*, Bignante EA* (2022) Aβ promotes amyloidogenic processing of APP and intracellular accumulation of Aβ42 through Go/Gβγ signaling. Front Cell Develop Biol, april 22, vol 10, art 852738, https://doi.org/10.3389/fcell.2022.852738 (IF2021-22: 6.68)
- Magdalena Antonino, Paula Marmo, Carlos Leandro Freites, Gonzalo Quassollo, Maria Florencia Sanchez, Alfredo Lorenzo*, Elena Anahí Bignante* (2021). Aβ promotes amyloidogenic processing of APP through a Go/Gβγ signaling. bioRxiv https://doi.org/10.1101/2021.03.10.434768 (una versión modificada de este trabajo se publicó posteriormente en Front Cell Develop Biol)
- Sigwald EL, de Olmos S, Lorenzo A. (2020) Retrograde and anterograde contextual fear amnesia induced by selective elimination of layer IV-Va neurons in the granular retrosplenial cortex (A29). Neurobiol. Learn Mem 2020 Apr 11:107229. doi: 10.1016/j.nlm.2020.107229
- Sigwald EL, Bignante EA, de Olmos S, Lorenzo A. (2019) Fear-context association during memory retrieval requires input from granular to dysgranular retrosplenial cortex. Neurobiol. Learn Mem 2019 Sep;163:107036. doi: 10.1016/j.nlm.2019.107036.
- Complete and updated list available here.
