Mechanism of neurodegeneration in Alzheimer´s disease
Alzheimer´s disease (AD) is the main cause of dementia in elderly people and the incidence is raising due to the sustained expansion of life expectancy in humans. Among the 10 most prevalent causes of death in adults, AD is the only one without effective treatment or prevention.
Progressive neuronal degeneration and death in brain areas involved in memory processing characterizes AD pathology. Therefore, understanding the mechanism of neuronal death in AD might lead to effective treatment to slow the progression of the pathology.
Accumulation of Amyloide beta (Aβ) in the brain is a critical step that leads to neuronal dysfunction and death. However, despite a significant effort from many scientific laboratories worldwide, the mechanism of Aβ toxicity remains elusive.
Our work focus on the study of the Amyloid β Precursor protein (APP) as a receptor for Aβ and the signaling pathways linked to neuronal death in AD. This knowledge might be useful for developing therapeutics for AD.
On the other hand, increasing evidence suggest that the retrosplenial cortex (RSC) is a cortical area early damaged in AD. RSC participates in processing episodic and spatial memories. Increasing evidence suggest that dysfunction of RSC could explain early memory failure in preclinical stages of AD. We are interested in addressing the anatomofunctional organization of RSC during memory processing by using a non-invasive approach that allows eliminating selective neuronal populations of RSC. This knowledge could be relevant for elucidating the contribution of RSC to early clinical symptoms of AD.
Student de Biología FCEFyN-UNC. Becaria CIN
PUBLICATIONS (parcial list)
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 May; 171:107229. doi: 10.1016/j.nlm.2020.107229. Epub 2020 Apr 11
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. Epub 2019 Jun 12.
Bignante EA, Lorenzo A (2018) APP signaling in Alzheimer’s disease. Aging https://doi.org/10.18632/aging.101641
Zamponi E, Zamponi N, Coskun P, Quassollo G, Lorenzo A, Cannas SA, Pigino G, Chialvo D, Gardiner K, Busciglio J, Helguera P (2018). Sustained NRF2 stabilization prevents critical oxidative damage in Down syndrome cells. Aging Cell 2018;e12812. https://doi.org/10.1111/acel.12812
Bignante EA, Ponce NE, Heredia F, Musso J, Krawczyk MC, Millán J, Pigino GF, Inestrosa NC, Boccia MM, Lorenzo A (2018) APP/Go protein Gβγ complex signaling mediates Aβ degeneration and cognitive impairment in Alzheimer´s disease models. Neurobiol Aging 64, 44-57
Zamponi E, Buratti F, Cataldi G, Caicedo HH, Song Y, Jungbauer LM, LaDu MJ, Bisbal M, Lorenzo A, Ma J, Helguera PR, Morfini GA, Brady ST, Pigino GF (2017) Prion protein inhibits fast axonal transport through a mechanism involving casein kinase 2. PLoS One 12(12):e0188340. doi: 10.1371/journal.pone.0188340. eCollection 2017
Sosa LJ, Caceres A, Dupraz S, Oksdath M, Quiroga S, Lorenzo A (2017) The physiological role of the Amyloid Precursor Protein (APP) as an adhesion molecule in the developing nervous system. J. Neurochem DOI: 10.1111/jnc.14122
Ramírez VT, Ramos-Fernández E, Henríquez JP, Lorenzo A, Inestrosa NC (2016). Wnt-5a/Frizzled9 receptor signaling through the Gαo/Gβγ complex regulates dendritic spine formation. J. Biol. Chem. 291(36):19092-107. doi: 10.1074/jbc.M116.722132.
Sigwald EL, Genoud ME, Giachero M, de Olmos S, Molina VA and Lorenzo A (2016). Selective degeneration of layer IV neurons in the granular retrosplenial cortex impairs the recall of contextual fear memory. Brain Struct Funct. 221(4), 1861- 1875. DOI 10.1007/s00429-015-1008-9
Bignante A, Heredia F, Morfini G, Lorenzo A. (2013) Amyloid Precursor protein (APP) and neurodegeneration in Alzheimer´s disease. Neurobiol Aging 3, 2525-2537.