ABSTRACT Alzheimer’s disease (AD) is a progressive neurodegenerative disease increasing in frequency as life expectancies increase. It has recently been estimated that approximately 10% of Type 2 diabetes (T2D) patients also develop AD-like symptoms and progress though similar stages of cognitive, memory and physical decline. The present review focuses on a thus far overlooked contributor to the pathologies seen in both AD and T2D, the renin-angiotensin system (RAS). The RAS controls a number of classic regulatory processes including blood pressure maintenance, body water balance, vasopressin and aldosterone release. However, some components can promote pathophysiological dysfunctions including inflammation, fibrosis and disrupted cell proliferation. There is a strong correlation between organs vulnerable to diabetic-induced hyperglycemic injury (eg. kidney and retina) and over activity of local tissue RASs. Also, insulin receptors and their down-stream signaling pathways are distributed in brain structures in which insulin-like growth factor (IGF) activation is of critical importance with regard to central functions. These functions include neurite outgrowth, synaptogenesis, stem cell differentiation, neuronal plasticity, learning and memory. Thus, dysfunctions associated with insulin signaling and metabolism can precipitate pathologies. This review describes current FDA-approved drugs to treat AD, biomarkers associated with dementia, the RAS and its role in the development of T2D-induced dementia, and efforts to develop small molecule angiotensin analog mimetics directed at RAS components capable of combating dementia via activation of the brain hepatocyte growth factor/Met receptor system.
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