Amylin in Alzheimer's disease: Pathological peptide or potential treatment?

Mietlicki‐Baase, Elizabeth G.

doi:10.1016/j.neuropharm.2017.12.016

Cited by 24 publications

(12 citation statements)

References 163 publications

(250 reference statements)

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“…The links between IAPP and AD have not gone unnoticed, with some authors presenting relevant reviews on the topic and hinting at possible therapeutic strategies (Despa and Decarli, 2013;Jackson et al, 2013;Bharadwaj et al, 2017;Mietlicki-Baase, 2018). The role of IAPP is undeniably relevant in both diabetes and AD.…”

Section: Strategies For Reducing Iapp Proteotoxicity Using Natural Comentioning

confidence: 99%

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

Raimundo

Ferreira

Martins

et al. 2020

Front. Mol. Neurosci.

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Diabetes affects hundreds of millions of patients worldwide. Despite the advances in understanding the disease and therapeutic options, it remains a leading cause of death and of comorbidities globally. Islet amyloid polypeptide (IAPP), or amylin, is a hormone produced by pancreatic β-cells. It contributes to the maintenance of glucose physiological levels namely by inhibiting insulin and glucagon secretion as well as controlling adiposity and satiation. IAPP is a highly amyloidogenic polypeptide forming intracellular aggregates and amyloid structures that are associated with β-cell death. Data also suggest the relevance of unprocessed IAPP forms as seeding for amyloid buildup. Besides the known consequences of hyperamylinemia in the pancreas, evidence has also pointed out that IAPP has a pathological role in cognitive function. More specifically, IAPP was shown to impair the blood-brain barrier; it was also seen to interact and co-deposit with amyloid beta peptide (Aß), and possibly with Tau, within the brain of Alzheimer's disease (AD) patients, thereby contributing to diabetes-associated dementia. In fact, it has been suggested that AD results from a metabolic dysfunction in the brain, leading to its proposed designation as type 3 diabetes. Here, we have first provided a brief perspective on the IAPP amyloidogenic process and its role in diabetes and AD. We have then discussed the potential interventions for modulating IAPP proteotoxicity that can be explored for therapeutics. Finally, we have proposed the concept of a "diabetes brain phenotype" hypothesis in AD, which may help design future IAPP-centered drug developmentstrategies against AD.

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Section: Strategies For Reducing Iapp Proteotoxicity Using Natural Comentioning

confidence: 99%

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

Raimundo

Ferreira

Martins

et al. 2020

Front. Mol. Neurosci.

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“…Amylin crosses the blood-brain barrier (BBB) [157][158][159], and its aggregate deposition is found in the brains of type II diabetes patients with AD [121]. The mechanisms underlying the pathological [122,123] and suppressive [117][118][119][120] effects of amylin to AD remain controversial [160].…”

Section: Aggregation Inhibition By Synthetic Polymersmentioning

confidence: 99%

High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways

Watanabe‐Nakayama

Sahoo

Ramamoorthy

et al. 2020

IJMS

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Individual Alzheimer’s disease (AD) patients have been shown to have structurally distinct amyloid-β (Aβ) aggregates, including fibrils, in their brain. These findings suggest the possibility of a relationship between AD progression and Aβ fibril structures. Thus, the characterization of the structural dynamics of Aβ could aid the development of novel therapeutic strategies and diagnosis. Protein structure and dynamics have typically been studied separately. Most of the commonly used biophysical approaches are limited in providing substantial details regarding the combination of both structure and dynamics. On the other hand, high-speed atomic force microscopy (HS-AFM), which simultaneously visualizes an individual protein structure and its dynamics in liquid in real time, can uniquely link the structure and the kinetic details, and it can also unveil novel insights. Although amyloidogenic proteins generate heterogeneously aggregated species, including transient unstable states during the aggregation process, HS-AFM elucidated the structural dynamics of individual aggregates in real time in liquid without purification and isolation. Here, we review and discuss the HS-AFM imaging of amyloid aggregation and strategies to optimize the experiments showing findings from Aβ and amylin, which is associated with type II diabetes, shares some common biological features with Aβ, and is reported to be involved in AD.

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“…[6] The previous reports indicate both the harmful and beneficiary character of hIAPP in AD. [7][8][9] Thus, there is a need to achieve a proper structural understanding of hIAPP as a risk factor in AD.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous Detection of Tyrosine and Structure‐Specific Intrinsic Fluorescence in the Fibrillation of Alzheimer's Associated Peptides

2020

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Understanding of the structural changes during their aggregation and interaction is a prerequisite for establishing the precise clinical relevance of human islet amyloid polypeptide (hIAPP) (involved in Type-II Diabetes Mellitus) in the treatment of Alzheimer's disease stemmed from beta-amyloid (Aβ). Herein, we show that the steady-state emission spectra obtained from photoluminescence (PL) simultaneously capture both the tyrosine derivative (tyrosinate) and the structure-specific intrinsic fluorescence during the aggregation of Aβ and hIAPP. We observe multiple peaks in the emission spectra which exist for structure-specific intrinsic fluorescence, and use the second derivative UV-Vis spectra and the shift in the tyrosine peak as a quantitative measure of the dissimilitude in the electronic states and the fibril growth. We further applied these techniques to detect the static electric field (0, 40, 120, 200 V/cm) induced promotion and inhibition of fibrillation in Aβ, hIAPP and their electric field dependent role in the fibrillation of Aβ : hIAPP(1 : 1). The results were corroborated by field-emission scanning electron microscopy (FESEM), and the determinations of secondary structures by Fourier transform infrared spectroscopy (FTIR). The results indicate that the emission spectrum can be used as a sensor to detect the presence of fibrils; hence for screening potential inhibitors of amyloid fibrillation.

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Amylin in Alzheimer's disease: Pathological peptide or potential treatment?

Cited by 24 publications

References 163 publications

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways

Simultaneous Detection of Tyrosine and Structure‐Specific Intrinsic Fluorescence in the Fibrillation of Alzheimer's Associated Peptides

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