Alterations of brain insulin signalling are a common pathophysiological mechanism leading to dementia in Alzheimer disease (AD) and Type 2-Diabetes Mellitus (T2DM). Brain insulin signalling acts as a key regulator for gene expression and cellular metabolism, both events sustaining neuronal activity and synaptic plasticity mechanisms. The actions of insulin in the brains of healthy individuals include central modulation of body metabolism and enhancement or regulation of memory and learning functions. Moreover, brain insulin controls oxidative metabolism via mitochondrial dynamics, thus protecting neurons against oxidative damage. Alterations of brain insulin signalling were associated with a higher risk to develop age-related cognitive decline and neurodegenerative diseases.
The overarching goal of our laboratory is to use multidisciplinary approaches to clarify the molecular mechanisms associated with the cell stress response during ageing and neurodegeneration.
In particular, the research work mainly focuses on:
Evaluating the role of oxidative stress in promoting protein and lipids damage in the brain during ageing and neurodegenerative disorders ;
Clarifying the role of insulin signaling pathway in modulating brain metabolism, by unraveling how defects of brain insulin signaling are associated with the development of AD-like pathology;
Understanding the impact of metabolic disease (type 2 diabetes mellitus/obesity) on AD and DS;
Evaluating the content of plasma-resident neuronal derived exosomes (NDE) isolated from AD and DS subjects, to identify biomarkers of insulin signaling alterations in the brain of living subjects;
Testing the efficacy of drugs administered through the intranasal route in recovering brain functions from AD-like neuropathology.