Identification of the major amyloid β-peptide-degrading enzyme in brain

2000 ◽  
Vol 38 ◽  
pp. S124
Author(s):  
N Iwata
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Degrading Enzyme

scholarly journals The Catalytic Domain of Insulin-degrading Enzyme Forms a Denaturant-resistant Complex with Amyloid β Peptide

2008 ◽  
Vol 283 (25) ◽  
pp. 17039-17048 ◽  
Author(s):  
Ramiro E. Llovera ◽  
Matías de Tullio ◽  
Leonardo G. Alonso ◽  
Malcolm A. Leissring ◽  
Sergio B. Kaufman ◽  
...  
Keyword(s):  
Catalytic Domain ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

scholarly journals Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria

2004 ◽  
Vol 383 (3) ◽  
pp. 439-446 ◽  
Author(s):  
Malcolm A. LEISSRING ◽  
Wesley FARRIS ◽  
Xining WU ◽  
Danos C. CHRISTODOULOU ◽  
Marcia C. HAIGIS ◽  
...  
Keyword(s):  
Fluorescent Protein ◽  
Late Onset ◽  
Amyloid Β ◽  
Type Ii Diabetes Mellitus ◽  
Allelic Association ◽  
Amyloid Β Peptide ◽  
Mitochondrial Targeting ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme

IDE (insulin-degrading enzyme) is a widely expressed zinc-metallopeptidase that has been shown to regulate both cerebral amyloid β-peptide and plasma insulin levels in vivo. Genetic linkage and allelic association have been reported between the IDE gene locus and both late-onset Alzheimer's disease and Type II diabetes mellitus, suggesting that altered IDE function may contribute to some cases of these highly prevalent disorders. Despite the potentially great importance of this peptidase to health and disease, many fundamental aspects of IDE biology remain unresolved. Here we identify a previously undescribed mitochondrial isoform of IDE generated by translation at an in-frame initiation codon 123 nucleotides upstream of the canonical translation start site, which results in the addition of a 41-amino-acid N-terminal mitochondrial targeting sequence. Fusion of this sequence to the N-terminus of green fluorescent protein directed this normally cytosolic protein to mitochondria, and full-length IDE constructs containing this sequence were also directed to mitochondria, as revealed by immuno-electron microscopy. Endogenous IDE protein was detected in purified mitochondria, where it was protected from digestion by trypsin and migrated at a size consistent with the predicted removal of the N-terminal targeting sequence upon transport into the mitochondrion. Functionally, we provide evidence that IDE can degrade cleaved mitochondrial targeting sequences. Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria.

scholarly journals Statins Promote the Degradation of Extracellular Amyloid β-Peptide by Microglia via Stimulation of Exosome-associated Insulin-degrading Enzyme (IDE) Secretion

2010 ◽  
Vol 285 (48) ◽  
pp. 37405-37414 ◽  
Author(s):  
Irfan Y. Tamboli ◽  
Esther Barth ◽  
Leonie Christian ◽  
Martin Siepmann ◽  
Sathish Kumar ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Insulin Degrading Enzyme ◽  
Degrading Enzyme ◽  
Stimulation Of

Amyloid β-peptide and Alzheimer's disease

2014 ◽  
Vol 56 ◽  
pp. 99-110 ◽  
Author(s):  
David Allsop ◽  
Jennifer Mayes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Senile Plaques ◽  
Strong Support ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Cascade Hypothesis ◽  
Sequence Of Events ◽  
Aβ Amyloid ◽  
Amyloid Cascade

One of the hallmarks of AD (Alzheimer's disease) is the formation of senile plaques in the brain, which contain fibrils composed of Aβ (amyloid β-peptide). According to the ‘amyloid cascade’ hypothesis, the aggregation of Aβ initiates a sequence of events leading to the formation of neurofibrillary tangles, neurodegeneration, and on to the main symptom of dementia. However, emphasis has now shifted away from fibrillar forms of Aβ and towards smaller and more soluble ‘oligomers’ as the main culprit in AD. The present chapter commences with a brief introduction to the disease and its current treatment, and then focuses on the formation of Aβ from the APP (amyloid precursor protein), the genetics of early-onset AD, which has provided strong support for the amyloid cascade hypothesis, and then on the development of new drugs aimed at reducing the load of cerebral Aβ, which is still the main hope for providing a more effective treatment for AD in the future.

Insights into amyloid disease from fly models

2014 ◽  
Vol 56 ◽  
pp. 69-83 ◽  
Author(s):  
Ko-Fan Chen ◽  
Damian C. Crowther
Keyword(s):  
Drosophila Melanogaster ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Disease Pathogenesis ◽  
Amyloid Aggregates ◽  
Aβ Amyloid ◽  
Polypeptide Chains ◽  
Amyloid Diseases

The formation of amyloid aggregates is a feature of most, if not all, polypeptide chains. In vivo modelling of this process has been undertaken in the fruitfly Drosophila melanogaster with remarkable success. Models of both neurological and systemic amyloid diseases have been generated and have informed our understanding of disease pathogenesis in two main ways. First, the toxic amyloid species have been at least partially characterized, for example in the case of the Aβ (amyloid β-peptide) associated with Alzheimer's disease. Secondly, the genetic underpinning of model disease-linked phenotypes has been characterized for a number of neurodegenerative disorders. The current challenge is to integrate our understanding of disease-linked processes in the fly with our growing knowledge of human disease, for the benefit of patients.

Analytical methods to explore Amyloid-β-Peptide variants beyond Aβ1-40 and Aβ1-42

2015 ◽  
Vol 48 (06) ◽  
Author(s):  
H Esselmann ◽  
C Hafermann ◽  
O Jahn ◽  
I Kraus ◽  
J Vogelgsang ◽  
...  
Keyword(s):  
Analytical Methods ◽  
Amyloid Β ◽  
Amyloid Β Peptide

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

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