Recent Advances in the Discovery of Therapeutics to Curtail Islet Amyloid Polypeptide Aggregation for Type 2 Diabetes Treatment

Smith, Alyssa A.; Moore, Kendall B. E.; Ambs, Patrick M.; Saraswati, A Prasanth; Fortin, Jessica S.

doi:10.1002/adbi.202101301

Cited by 3 publications

(6 citation statements)

References 150 publications

(206 reference statements)

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“…Also, cell viability assays proved that the protection effect on pancreatic INS-1 cells imposed by these compounds in T2D patients follows the order caffeic acid > chlorogenic acid > caffeine . Cichoric acid, a derivative of caffeic acid, also targets the residues of hIAPP via electrostatic and π–π stacking . Brazilin has also displayed amyloid inhibition, delay of conformational transition, and fibril disruption of hIAPP and Aβ .…”

Section: Anti-amyloid Activity Of Natural Polyphenolsmentioning

confidence: 99%

“…Other green tea extracts, such as catechin, epicatechin, gallocatechin gallate (GCG), epicatechin gallate (ECG), and epigallocatechin (EGC) (Figure ), also display anti-amyloidogenic properties by directly binding with the steric zipper of the fibrillar segments to freeze fibrillation . A molecular dynamics (MD) study showed that the ability of three stereoisomeric catechins to disrupt and bind with Aβ 42 protofibrils follows the order (−)-catechin > (+)-catechin > epicatechin (Figure ).…”

Section: Anti-amyloid Activity Of Natural Polyphenolsmentioning

confidence: 99%

“…Compounds like azadirachtin (found in neem seeds) and other neem extracts directly disaggregate hIAPP and tau fibrils, respectively. , Arg11 and His18 of hIAPP interact with heme, which interrupts the formation of β-sheet structures. Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid derived from Boswellia serrata extracts, reduces the cerebral Aβ levels and plaque burden …”

Section: Anti-amyloid Activity Of Other Small Moleculesmentioning

confidence: 99%

“…To date, a massive amount of molecules including small molecular probes, peptides and peptidomimetics, antibodies, antibiotics, nanoparticles, and polymeric materials have been shown to effectively inhibit aggregation. − Out of these, small molecules are the most versatile in their inhibitory function. Among the small molecules, the natural products possess good pharmacological activities, less cytotoxicity, and immunogenicity. , The natural products stabilize monomers, inhibit nucleation, lead toxic oligomers into off-pathway aggregation, and disrupt amyloid fibrils, thus targeting amyloid peptides at various stages. ,− They also influence secondary processes, such as oxidative stress, inflammation, and protein homeostasis .…”

Section: Introductionmentioning

confidence: 99%

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Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

Roy

Paul

2023

J. Phys. Chem. B

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The onset of amyloidogenic diseases is associated with the misfolding and aggregation of proteins. Despite extensive research, no effective therapeutics are yet available to treat these chronic degenerative diseases. Targeting the aggregation of disease-specific proteins is regarded as a promising new approach to treat these diseases. In the past few years, rapid progress in this field has been made in vitro, in vivo, and in silico to generate potential drug candidates, ranging from small molecules to polymers to nanoparticles. Small molecular probes, mostly those derived from natural sources, have been of particular interest among amyloid inhibitors. Here, we summarize some of the most important natural small molecular probes which can inhibit the aggregation of Aβ, hIAPP, and α-syn peptides and discuss how their binding efficacy and preference for the peptides vary with their structure and conformation. This provides a comprehensive idea of the crucial factors which should be incorporated into the future design of novel drug candidates useful for the treatment of amyloid diseases.

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Section: Anti-amyloid Activity Of Natural Polyphenolsmentioning

confidence: 99%

Section: Anti-amyloid Activity Of Natural Polyphenolsmentioning

confidence: 99%

Section: Anti-amyloid Activity Of Other Small Moleculesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

Roy

Paul

2023

J. Phys. Chem. B

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“…The primary sequence of the peptide is extremely conserved in organisms, for example, human and mouse IAPPs differ by only six amino acids. The formation of IAPP deposits is intrinsically associated with type 2 diabetes (T2D) because more than 70% diabetic patients present this type of amyloid formation [ 32 ]. The number of aggregates appears to be correlated with the pathology severity, as evidenced by autopsies.…”

Section: The Hallmark Lesions Of Ad: β-Amyloid and Tau Proteinsmentioning

confidence: 99%

From Small Peptides to Large Proteins against Alzheimer’sDisease

et al. 2022

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Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the elderly. The two cardinal neuropathological hallmarks of AD are the senile plaques, which are extracellular deposits mainly constituted by beta-amyloids, and neurofibrillary tangles formed by abnormally phosphorylated Tau (p-Tau) located in the cytoplasm of neurons. Although the research has made relevant progress in the management of the disease, the treatment is still lacking. Only symptomatic medications exist for the disease, and, in the meantime, laboratories worldwide are investigating disease-modifying treatments for AD. In the present review, results centered on the use of peptides of different sizes involved in AD are presented.

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Type‐2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease

Leibold

Bain

Despa

2023

Molecular Nutrition Food Res

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Type‐2 diabetes raises the risk for Alzheimer's disease (AD)‐type dementia and the conversion from mild cognitive impairment to dementia, yet mechanisms connecting type‐2 diabetes to AD remain largely unknown. Amylin, a pancreatic β‐cell hormone co‐secreted with insulin, participates in the central regulation of satiation, but also forms pancreatic amyloid in persons with type‐2 diabetes and synergistically interacts with brain amyloid β (Aβ) pathology, in both sporadic and familial Alzheimer's disease (AD). Growing evidence from studies of tumor growth, together with early observations in skeletal muscle, indicates amylin as a potential trigger of cellular metabolic reprogramming. Because the blood, cerebrospinal fluid, and brain parenchyma in humans with AD have increased concentrations of amylin, amylin‐mediated pathological processes in the brain may involve neuronal metabolic remodeling. This review summarizes recent progress in understanding the link between prediabetic hypersecretion of amylin and risk of neuronal metabolic remodeling and AD and suggests nutritional and medical effects of food constituents that might prevent and/or ameliorate amylin‐mediated neuronal metabolic remodeling.

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Recent Advances in the Discovery of Therapeutics to Curtail Islet Amyloid Polypeptide Aggregation for Type 2 Diabetes Treatment

Abstract: Table 2. Continued.

Cited by 3 publications

References 150 publications

Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

Illustrating the Effect of Small Molecules Derived from Natural Resources on Amyloid Peptides

From Small Peptides to Large Proteins against Alzheimer’sDisease

Type‐2 Diabetes, Pancreatic Amylin, and Neuronal Metabolic Remodeling in Alzheimer's Disease

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