Brain insulin signaling in Alzheimer's disease

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2016-2017Alzheimer’s disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia affecting elderly people. Its pathological hallmarks are the presence of extracellular aggregates of amyloid-β peptide (Aβ), also known as senile plaques, and intracellular clusters of hyperphosphorylated tau protein, commonly called neurofibrillary tangles (NFTs). Classically, the brain was considered to be insulin-insensitive, but evidence has proved the contrary and now it is widely accepted that insulin and IGF-1 have neuromodulatory actions. Insulin signaling is involved in various neuronal functions such as synapse transmission, cognition, learning and memory. Insulin resistance, together with AβOs neurotoxicity, neuronal metabolic stress and neuroinflammation, has been shown to play a role in AD pathogenesis. In this review we will describe the connection between neuronal insulin signaling and the pathogenesis and progression of AD, as well as the new promising therapeutic approaches focused on the insulin signaling pathway that are being researched, such as intranasal insulin or insulin sensitizing agents