Joanne Elizabeth Rowles, Kevin Noel KeanE, Thiago Gomes Heck, Vinicius Cruzat, Giuseppe Verdile and Philip Newsholme.
School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences, Curtin University, Perth 6102, Australia; joanne.pradella@postgrad.curtin.edu.au (J.E.R.); kevin.keane@curtin.edu.au (K.N.K.); giuseppe.verdile@curtin.edu.au (G.V.); Philip.newsholme@curtin.edu.au (P.N.)
Physiology Research Group, Graduate Program in Integral Attention to Health (PPGAIS-UNIJUÍ/UNICRUZ) and Graduate Program in Mathematical and Computational Modeling, Regional University of Northwestern Rio Grande do Sul State (UNIJUÍ), Ijuí, RS 98700-000, Brazil; thiago.heck@unijui.edu.br
Faculty of Health, Torrens University Australia, Melbourne 3000, Australia
School of Medical and Health Sciences, Edith Cowan University, Joondalup 6027, Australia, Correspondence: vinicius.cruzat@laureate.edu.au; Tel.: +61-(03)-9415-3362
ABSTRACT
Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (β-Amyloid; Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD.
INTODUCTION
Alzheimer’s disease (AD) and type 2 diabetes (T2D) are two of the most widespread age-related chronic diseases, and the prevalence of both is steadily increasing. AD and T2D share similar risk factors, which can include a sedentary lifestyle, poor diet, obesity, and hereditary predisposition. Studies have shown that patients with T2D are up to 65% more likely to develop AD than non-diabetic patients, while AD individuals are more likely to be insulin resistant. T2D and AD also share dysfunctions in the insulin receptor, chronic inflammation, and secretion of amyloidogenic peptides.