Neuronal differentiation and brain aging

Molecular and Cellular Neurobiology
Centro de Biología Molecular “Severo Ochoa” CSIC-UAM (CBMSO)

The general aim of the laboratory is to understand the mechanisms behind the decline in cognitive capacity that occurs during aging. Cognitive decline is not identical in all individuals and clear associations exist between the rate and severity of cognitive decline and the individual’s heritable traits and lifestyle. At the molecular level, the aging phenotype is the consequence of a combination of deficits at multiple levels: mitochondria, protein synthesis and protein quality control machineries, degradation of cellular waste, carbohydrate and triglyceride metabolic pathways for ATP production, hormone synthesis, stem cell renewal, cell membrane organization. In most individuals brain cells cope relatively well with these deficits, only resulting in the mild and common symptoms of aging, such as forgetfulness, decreased ability to maintain focus and decreased problem solving capability. In many others however, these changes accumulate and progress resulting in more serious symptoms and conditions, such as dementia and depression or even Alzheimer’s disease. It then appears that the fine dissection of the causes and mechanisms behind cognitive decay in the aged that we pursue, may facilitate the understanding of the causes and mechanisms involved in pathological cognitive decay. We approach this question by investigating, through biochemical, molecular, electrophysiological and behavioral approaches, the effect of aging on neuronal plasma membrane-mediated survival and function signaling. Some of our contributions to the field in the recent years are: Sodero et al., (2012) EMBO J. 31: 1764-1773; Guix et al., (2012) EMBO Mol Med. 4: 660-673; Trovò et al (2013) Nature Neurosci. 16, 449-455; Martin et al. (2014). EMBO Mol. Med. 6, 902-917; Brachet et al. (2015)  J. Cell Biol. 208(6):791-806; Palomer et al. (2016) Nature Comm. 7, 11081-11086; Palomer et al., (2016) Cell Reports 2016;16(11):2889-900, Benvegnù, et al., (2017) Molecular Cell, 66(3), 358-372, Salas et al., (2018) Neurobiol Dis. 113:82-96; Martín-Segura et al., (2019) Aging Cell 18(3):e12932, Casadomé-Perales et al. (2019) Nanomedicine doi: 10.2217/nnm-2018-0496, de Vidania et al. (2020) Front. Neurosci. 14:562581.doi: 10.3389/fnins.2020.562581; Guix et al. (2021) Life Sci. Alliance. 4(8):e202101055. doi: 10.26508/lsa.

Molecular Biomedicine