Mitochondria and Neurodegenerative Disorders

Overview

Our group has achieved acknowledged contributions in understanding early cellular mechanisms related with mitochondrial deregulation and neuronal signaling pathways in neurodegenerative conditions. The group aligns the interest in understanding the impact of mitochondrial (de)regulation, redox signaling and the activity of glutamatergic postsynapses, with the modulation of cell senescent markers in initial stages of neurodegenerative disorders. We resort to biochemistry, cellular and molecular biology, imaging, electron microscopy and other techniques to analyze how neuronal communication and survival is affected specifically in rodent and human models of Huntington’s disease (HD), a genetic disorder caused by expansion of CAG repeats, and Alzheimer’s disease (AD), the most prevalent age-related brain disorder. Different therapeutic approaches have been also investigated in these brain pathologies. In HD we found early mitochondrial and redox modifications in both human and mouse brains and peripheral cells [doi: 10.1016/j.redox.2022.102424], and early striatal structural changes and neurometabolic alterations in HD mouse model [doi: 10.1093/hmg/ddy119]. Therapeutic approaches targeting mitochondria were assessed by enhancing mitochondrial sirtuin 3 [doi: 10.1016/j.freeradbiomed.2020.11.031], activating the sigma-1 receptor with pridopidine [doi: 10.1007/s13311-021-01022-9] or restoring the active form of Src kinase family [doi: 10.1089/ars.2022.0001]; extracellular vesicles were also demonstrated to improve GABAergic transmission in HD human-like neurons [doi: 10.7150/thno.81981]. By investigating AD early pathogenesis and neuroprotection we defined the impact of chronic hyperglycemia on adult hippocampal neurogenesis and memory [doi: 10.1016/j.neurobiolaging.2020.04.003] and how modulating epigenetis by decreasing the activity and/or expression of class I histone deacetylases influences ER-mitochondria crosstalk [doi: 10.1111/acel.13895].