Role of endocannabinoids modulation in autophagy and inflammatory mechanisms underlying Alzheimer's disease.
Alzheimer's disease (AD) affects about 600,000 people in Italy and constitutes one of the most serious problems of social medicine. The few therapies approved so far are poorly effective and only at the initial stages of the disease. It is therefore urgent to find strategies capable of slowing the disease.
Glial activation, increased neuroinflammation and changes in metabolic functions characterize the development of AD. Much interest is focusing on endocannabinoids (ECB), especially for their ability to counteract neuroinflammation.
Aim of the project will be: i) to evaluate the efficacy of FAAH, a pharmacological inhibitor of hydrolase involved in the catabolism of ECB, in restoring autophagy, which is involved in the clearance of the amyloid peptide and is reduced in AD; 2) since we recently discussed the potential of some foods derived from plants to increase the ECB tone, we will evaluate green extracts as a possible source of nutraceuticals to counteract neuroinflammation and enhance autophagy.
The experiments will be carried out in vitro, taking advantage of the murine BV2 microglia cell line, analyzing the pro and anti-inflammatory markers after treatment with amyloid peptide or with proinflammatory factors in the presence of FAAH or plant extracts using immunofluorescence, western blot, real -time PCR. Furthermore, the AD Tg2576 mice will be supplemented with FAAH or with plant extracts. Brain will be analyzed by immunohistochemistry, western blot, real-time PCR for the presence of amyloid plaques and the presence of activated microglia, analyzing its polarization towards a pro- or anti-inflammatory phenotype.
This project will allow to deepen the knowledge on the role of ECB in AD pathogenesis, and the development and production of innovative nutraceutical substances from natural sources and the creation of a controlled supply chain of various plants of food interest to be used as matrices for the production of nutraceuticals and functional foods.