The research group “Mitochondria and Neurodegenerative Disorders” is focused on understanding cellular and molecular mechanisms associated to mitochondria in early stages of brain neurodegenerative disorders, namely in Huntington’s (HD), Alzheimer’s (AD) and Parkinson’s (PD) diseases. These are chronic, debilitating and age-related brain disorders, characterized by selective cerebral neurodegeneration and cognitive decline. Modified, misfolded and/or mutant proteins affected in these diseases interfere with neuronal function, potentially causing deregulated mitochondrial function and bioenergetics, and altered intracellular redox signaling, namely after activation of glutamate synapses, or lead to defective neurogenesis, impacting on brain cognitive reserve. Although there are several mechanisms by which neurons degenerate, the initial pathways of neuronal dysfunction, occurring before main disease-related symptoms, are largely unknown for each disorder.
In this perspective, by using molecular, cellular, ex-vivo and in vivo approaches, we aim to investigate early modifications affecting mitochondrial function and related signaling linked to redox regulation, glutamate postsynaptic dysfunction and/or modified neurogenesis in different models of neurodegenerative disorders and in peripheral human cells derived from patients and non-affected individuals. The last envisages a closer interaction with the local hospital, particularly in HD and AD. Identification of early disease mechanisms are envisaged to uncover relevant molecular targets for therapeutic intervention, as reviewed by us (Naia et al., 2017, Biochem. Biophys. Res. Commun). Therefore, the group aligns basic and translational research with interest in early disease stages with investigation on neuroprotective therapies based on modifiers of mitochondrial function, glutamate synapse and neurogenesis, using pharmacological compounds, modulation of protein expression and/or gene correction strategies.
iPS cells-derived exosomes - impact on mitochondrial (dys)function in Huntington's disease and potential nanodelivery system for microRNA-based therapeutics, Fundação para a Ciência e a Tecnologia (FCT), Portugal, ref. POCI-01-0145-FEDER-029621 (2018-2021).
Transcriptional activity modulation in Alzheimer's disease by inhibitors of histone deacetylases, Fundação para a Ciência e a Tecnologia (FCT), ref. POCI-01-0145-FEDER-032316 (2018-2021)
Exploring striatal postsynaptic SAPAP3 in Huntington’s disease, EHDN-European Huntington’s Disease Network (2018-2019).
Exploring the role of pridopidine on mitochondrial function and dynamics in Huntington’s disease models, TEVA Pharmaceutical Industries Ltd., Petach Tikva, Israel (2017- 2018).
Creation and characterization of neural cells derived from pre-symptomatic and symptomatic Huntington´s disease patient-specific induced pluripotent stem cells”
Supported by: Fundação Luso-Americana para o Desenvolvimento (FLAD), Portugal FLAD LIFE SCIENCE 2020 - FLAD Grants on Portugal-USA collaborative translational project (2015–2017).