In Vivo 2-Deoxyglucose Administration Preserves Glucose and Glutamate Transport and Mitochondrial Function in Cortical Synaptic Terminals after Exposure to Amyloid β-Peptide and Iron: Evidence for a Stress Response

2000 ◽  
Vol 166 (1) ◽  
pp. 173-179 ◽  
Author(s):  
Zhi Hong Guo ◽  
Mark P. Mattson
Keyword(s):  
Stress Response ◽  
Mitochondrial Function ◽  
Amyloid Β ◽  
Glutamate Transport ◽  
Amyloid Β Peptide ◽  
Synaptic Terminals

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.

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.

scholarly journals In vivo oxidative stress in brain of Alzheimer disease transgenic mice: Requirement for methionine 35 in amyloid β-peptide of APP

2010 ◽  
Vol 48 (1) ◽  
pp. 136-144 ◽  
Author(s):  
D. Allan Butterfield ◽  
Veronica Galvan ◽  
Miranda Bader Lange ◽  
Huidong Tang ◽  
Renã A. Sowell ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer Disease ◽  
Transgenic Mice ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Methionine 35

scholarly journals Application of optogenetic Amyloid-β distinguishes between metabolic and physical damages in neurodegeneration

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Chu Hsien Lim ◽  
Prameet Kaur ◽  
Emelyne Teo ◽  
Vanessa Yuk Man Lam ◽  
Fangchen Zhu ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Biological Effects ◽  
Amyloid Β ◽  
Tissue Loss ◽  
Amyloid Β Peptide ◽  
Physical Damage ◽  
Living Tissues

The brains of Alzheimer’s disease patients show a decrease in brain mass and a preponderance of extracellular Amyloid-β plaques. These plaques are formed by aggregation of polypeptides that are derived from the Amyloid Precursor Protein (APP). Amyloid-β plaques are thought to play either a direct or an indirect role in disease progression, however the exact role of aggregation and plaque formation in the aetiology of Alzheimer’s disease (AD) is subject to debate as the biological effects of soluble and aggregated Amyloid-β peptides are difficult to separate in vivo. To investigate the consequences of formation of Amyloid-β oligomers in living tissues, we developed a fluorescently tagged, optogenetic Amyloid-β peptide that oligomerizes rapidly in the presence of blue light. We applied this system to the crucial question of how intracellular Amyloid-β oligomers underlie the pathologies of A. We use Drosophila, C. elegans and D. rerio to show that, although both expression and induced oligomerization of Amyloid-β were detrimental to lifespan and healthspan, we were able to separate the metabolic and physical damage caused by light-induced Amyloid-β oligomerization from Amyloid-β expression alone. The physical damage caused by Amyloid-β oligomers also recapitulated the catastrophic tissue loss that is a hallmark of late AD. We show that the lifespan deficit induced by Amyloid-β oligomers was reduced with Li+ treatment. Our results present the first model to separate different aspects of disease progression.

Amyloid imaging in dementia

2012 ◽  
Vol 23 (1) ◽  
pp. 43-60
Author(s):  
A Ashraf ◽  
P Mehta ◽  
P Edison
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Critical Evaluation ◽  
Amyloid Β ◽  
Amyloid Imaging ◽  
Therapeutic Window ◽  
Pharmacological Intervention ◽  
Early Event ◽  
Amyloid Β Peptide

SummaryA major advancement in the field of medicine has been the timely advent of amyloid imaging, which has allowed critical evaluation of the complex relationship between amyloid β peptide (Aβ) aggregation and Alzheimer's disease in vivo. Most importantly, amyloid imaging has the potential to detect Aβ in mildly affected as well as asymptomatic individuals, when the therapeutic window of opportunity might still be open to pharmacological intervention. It also shows significant promise in differential diagnosis of mild cognitive impairment or atypical dementias. Amyloid imaging studies support a model in which amyloid aggregation is considered an early event on the path of dementia, beginning insidiously in cognitively healthy individuals being accompanied by subtle cognitive, functional and structural brain alterations suggestive of incipient AD. As individuals progress to dementia, clinical decline and neurodegeneration accelerate and might proceed independently of amyloid accumulation. In this review we focus on amyloid imaging with particular emphasis on [11C]PIB in AD, mild cognitive impairment and other dementias, and discuss the advances made in this perplexing field.

scholarly journals Physiologically regulated transgenic ABCA1 does not reduce amyloid burden or amyloid-β peptide levels in vivo

2007 ◽  
Vol 48 (4) ◽  
pp. 914-923 ◽  
Author(s):  
Veronica Hirsch-Reinshagen ◽  
Jennifer Y. Chan ◽  
Anna Wilkinson ◽  
Tracie Tanaka ◽  
Jianjia Fan ◽  
...  
Keyword(s):  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Amyloid Burden

scholarly journals Covalent Protein Painting Reveals Structural Changes in the Proteome in Alzheimer Disease

2020 ◽  
Author(s):  
Casimir Bamberger ◽  
Sandra Pankow ◽  
Salvador Martínez-Bartolomé ◽  
Michelle Ma ◽  
Jolene Diedrich ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Chemical Modification ◽  
Succinate Dehydrogenase ◽  
Structural Changes ◽  
Amyloid Β ◽  
Lewy Body Disease ◽  
Structural Proteomics ◽  
Amyloid Β Peptide ◽  
Lysine Residues

AbstractThe 3D structures of aberrant protein folds have been visualized in exquisite detail, yet no method has been able to quantitatively measure protein misfolding across a proteome. Here, we present Covalent Protein Painting (CPP), a mass spectrometry-based structural proteomics approach to quantify the accessibility of lysine ε-amines for chemical modification at the surface of natively folded proteins. We used CPP to survey 2,645 lysine residues in the proteome of HEK293T cells in vivo and found that mild heat shock increased rather than decreased lysine accessibility for chemical modification. CPP was able to differentiate patients with Alzheimer disease (AD) or Lewy body disease (LBD) or both from controls based on relative accessibility of lysine residues K147, K137, and K28 in Tubulin-β, Succinate dehydrogenase, and amyloid-β peptide, respectively. The alterations of Tubulin-β and Succinate dehydrogenase hint to broader perturbations of the proteome in AD beyond amyloid-β and hyper-phosphorylated tau.

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