|
Strategic Objective
Oxidative stress is a key element in the aetiopathogenesis of neurodegenerative diseases and their comorbidities. Our laboratory studies the antioxidant protection mechanisms activated by extracellular signals and how this response ould be regulated pharmacologically to provide a therapeutic benefit in these diseases.
To meet these two objectives, we are studying signalling pathways that regulate antioxidant metabolism and provide a general protective response. An important finding of this group was the observation that the PI3K/AKT/GSK-3 survival pathway regulates the transcription factor NRF2, guardian of cellular redox homeostasis, that provides protection against oxidative, inflammatory and proteotoxic stress. For the past year we have been working on the validation this transcription factor as a new therapeutic target to modify progression of Parkinson’s and Alzheimer’s disease as well co-morbid retinopathy and type II diabetes.
Research Lines
• Role of oxidative stress in neuronal death and neuroinflammation in neurodegenerative diseases
• Validation of NRF2 as a new therapeutic target in neurodegenerative diseases.
• Use of NRF2 transcriptional signature as a biomarker of prognosis, progression and therapeutic efficacy.
• Identification of NRF2 activating compounds by inhibiting their interaction with β-TrCP
• Relevance of NRF2 transcriptional signature in altered molecular processes in ALS models
• Molecular basis of the role of Nrf2 in type 2 diabetes and its complications (diabetic retinopathy and nephropathy)
|