Abstract
Alzheimer's disease (AD) and type 2 diabetes are connected in a way that is still not completely understood, but insulin resistance has been implicated as a risk factor for developing AD. Here we show an evidence that insulin is capable of reducing cytotoxicity induced by Amyloid-beta peptides (A-beta) in its oligomeric form in a dose-dependent manner. By TUNEL and biochemical assays we demonstrate that the recovery of the cell viability is obtained by inhibition of intrinsic apoptotic program, triggered by A-beta and involving caspase 9 and 3 activation. A protective role of insulin on mitochondrial damage is also shown by using Mito-red vital dye. Furthermore, A-beta activates the stress inducible Hsp70 protein in LAN5 cells and an overexpression is detectable after the addition of insulin, suggesting that this major induction is the necessary condition to activate a cell survival program. Together, these results may provide opportunities for the design of preventive and therapeutic strategies against AD.
Highlights
Alzheimer’s disease (AD) is the most common form of dementia in the elderly
Alzheimer’s disease (AD) and type 2 diabetes are connected in a way that is still not completely understood, but insulin resistance has been implicated as a risk factor for developing AD
Neuronal degeneration occurs near the amyloid plaques, some studies have suggested that intermediates such as protofibrils or simple oligomers are involved in AD pathogenesis and even appear to be the more dangerous species in the onset of the pathology [3]
Summary
Alzheimer’s disease (AD) is the most common form of dementia in the elderly It is characterized by neuronal cell loss and progressive accumulation of neurofibrillary tangles (NFT) in neurons, and amyloid fibers in neuritic (senile) plaques and in the walls of blood vessels [1]. While the monomeric A-beta is not neurotoxic, under specific conditions it is able to misfold from its soluble form into small oligomers and highly ordered fibrillar aggregates. This phenomenon is known as the aggregation of proteins and it is a characteristic feature of several neurodegenerative diseases [2]. Neuronal degeneration occurs near the amyloid plaques, some studies have suggested that intermediates such as protofibrils or simple oligomers are involved in AD pathogenesis and even appear to be the more dangerous species in the onset of the pathology [3]
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