ABSTRACT
Alzheimer’s disease (AD) is the most common cause of dementia and is responsible for up to 75% of the nearly 47 million dementia cases worldwide. AD is the clinical manifestation of toxic β-amyloid and neurofibrillary tangles accumulation caused by altered proteostasis. Due to not fully understood molecular mechanisms of AD only symptomatic treatment is available. Considering that cognitive decline is associated with insulin resistance, metabolic alterations may be the primary causes of the AD and insulin therapy is proposed as a novel approach in AD treatment. Intranasal administration of insulin appears to be a profitable solution for drug delivery to the brain due to blood-brain barrier bypassing, higher bioavailability and the lack of systemic side effects. When applying this method, insulin is sprayed into the nasal cavity, enters the mucosa and is transported along the axon bundles to the brain. Clinical trials of AD treatment with intranasal insulin revealed improvement in cognition, verbal memory and functional status. Notably, enhancement in memory and cognition were observed both in healthy adults and in AD patients and were ApoE ε4-related. The use of cell-penetrating peptides (CPPs) improve cellular uptake of insulin, enhance bioavailability and increase the direct insulin transport into the deeper regions of the brain such as the olfactory bulb and hippocampus. Animal studies revealed beneficial effects on AD symptoms of other molecules applied in connection with CPPs and most of them approve CPPs formulations for use in clinical trials. This review article summarize clinical trials results of intranasal insulin administration in AD treatment and propose the use of CPPs as an additive to conventional and experimental therapies for AD.
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