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- Benedict, Christian, Docent, 1976-, et al.
(författare)
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Insulin Resistance as a Therapeutic Target in the Treatment of Alzheimer's Disease : A State-of-the-Art Review
- 2018
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Ingår i: Frontiers in Neuroscience. - : FRONTIERS MEDIA SA. - 1662-4548 .- 1662-453X. ; 12
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Forskningsöversikt (refereegranskat)abstract
- Research in animals and humans has shown that type 2 diabetes and its prodromal state, insulin resistance, promote major pathological hallmarks of Alzheimer's disease (AD), such as the formation of amyloid plaques and neurofibrillary tangles (NFT). Worrisomely, dysregulated amyloid beta (A beta) metabolism has also been shown to promote central nervous system insulin resistance; although the role of tau metabolism remains controversial. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted insulin signaling. They also provide strong support for the hypothesis that pharmacologically restoring brain insulin signaling could represent a promising strategy to curb the development and progression of AD. In this context, great hopes have been attached to the use of intranasal insulin. This drug delivery method increases cerebrospinal fluid concentrations of insulin in the absence of peripheral side effects, such as hypoglycemia. With this in mind, the present review will also summarize current knowledge on the efficacy of intranasal insulin to mitigate major pathological symptoms of AD, i.e., cognitive impairment and deregulation of A beta and tau metabolism.
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| 2. |
- Chapman, Colin D, et al.
(författare)
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Intranasal insulin in Alzheimer's disease : food for thought
- 2018
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Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 136, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests that disrupted brain insulin signaling promotes the development and progression of Alzheimer's disease (AD), driving clinicians to target this circuitry. While both traditional and more modern antidiabetics show promise in combating insulin resistance, intranasal insulin appears to be the most efficient method of boosting brain insulin. Furthermore, intranasal delivery elegantly avoids adverse effects from peripheral insulin administration. However, there remain significant open questions regarding intranasal insulin's efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review aims to critically evaluate the present evidence and future potential of intranasal insulin as a meaningful treatment for AD.
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