Neurodegenerative diseases include a group of pathologies of unknown etiology which usually exhibit very varied symptoms; a common feature to all of them is the progress of the disease which reflects the gradual disintegration of the nervous system. The outcome is the same in all cases: loss of neurons due to cell death. They are classified according to the clinical manifestations arising in each case, and so those that essentially show a dementia syndrome are distinct, the clearest example being Alzheimer’s disease (AD). Recently, we have described that (1-42) ß Amyloid peptide (Aß) involves the GTPase Rac1 in neuronal death and moreover we have also described that this GTPase Rac1 activates to glycogen phosphorylase (PYG) and regulates glycogenolysis in lymphocytes. Based on this, we hypothesize that a deregulated activity of Rac1 due to Aß could generate abnormal processes at cytoskeleton level or generating reactive oxygen species which would lead to a lost of neuronal adhesion capacity, oxidative stress, etc. which would result in neuronal death.
We work on:
- Examining whether Aß peptide signals to PYG through Rac1 and leads to glycogenolysis in neurons.
- Characterizing the Rac1 effector moleculaes which trigger neuronal death induced by Aß peptide. Role of oxidative stressand PYG in this process.
The knowledge generated from the previous objectives will be useful to tacked in vitro therapeutic strategies that will allow using organic molecules or permeable peptides to block at molecular level the death program induced by the Aß peptide.
The group received funding from: Fundación Gangoiti, Fundación Ikerbasque, ISCIII (PI15/00207)
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