Title : Brain insulin resistance in Alzheimer’s disease: can phytochemicals exert beneficial effects?
Abstract:
Abstract:Overnutrition and modern diets containing high proportions of saturated fat are amongst the major factors responsible for the development of low-grade, systemic, chronic inflammation, hyperglycaemia and dyslipidaemia. These conditions may eventually lead to insulin resistance (IR), a reduced ability of an organism to mount a normal and coordinated glucose lowering response via tissue-autonomous and crosstalk-dependent mechanisms. If established, IR predisposes affected and susceptible subjects to a cluster of metabolic disorders such as type II diabetes (T2DM) and cardiovascular diseases. Interestingly enough, recent studies started to recognize IR as a risk factor also for neurodegenerative conditions such as Alzheimer’s disease (AD) and other cognitive disorders. Coherently, over 80% of AD patients have T2DM or abnormal serum glucose levels, suggesting that the pathogenic mechanisms of IR and AD might well overlap. IR, indeed, plays a crucial role in the self-feeding cycle between chronic neuroinflammation, mitochondrial dysfunction and oxidative stress responsible for amyloid β-protein deposition and aberrant tau phosphorylation. Moreover, both insulin and amyloid β-protein are metabolized by insulin degrading enzyme and defects in this enzyme can be envisaged as one of the bases for the strong association between T2DM and AD. Furthermore, AD has been demonstrated to be associated with diminished insulin receptors by nearly 80%.
In these scenarios, the molecular interconnections between neuroinflammation and IR could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. Along these lines, increasing evidence suggest that improving metabolic impairments could be effective to reduce AD progression and ameliorate cognitive function. Originally considered ‘health-promoting’ by virtue of their radical-scavenging or direct antioxidant effects on cellular biomolecules, phytochemicals are now believed to effectively modulate the inflammatory response by intercepting reactive species at the level of critical signalling pathways. Coherently, growing evidence shows that certain dietary compounds (i.e., flavonoids, curcuminoids, stilbenes, phenolic acids, carotenoids) could play a beneficial role in neurodegenerative diseases.
This presentation aims to provide an updated vision on the impact of metabolic dysfunctions on AD with a focus on inflammation and IR as risk factors. Moreover, recent evidence on the most promising PhC-based, therapeutic interventions able to counteract AD by ameliorating and contrasting IR will also be presented.
What will audience learn from your presentation?
• Audience will get an updated vision of the mechanisms through which IR can be involved in AD development.
• The presentation is intended for scientists and physicians who work in the field of the interconnections between
metabolic dysfunctions and neurodegenerative diseases.
• The content of the presentation may be useful to open new perspectives aimed to develop new plant-based,
therapeutical tools.
