scholarly journals Copper Binding to the Amyloid-β (Aβ) Peptide Associated with Alzheimer's Disease

2004 ◽  
Vol 279 (18) ◽  
pp. 18169-18177 ◽  
Author(s):  
Christopher D. Syme ◽  
Rebecca C. Nadal ◽  
Stephen E. J. Rigby ◽  
John H. Viles
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Copper Binding

Affinity of Cu+for the Copper-Binding Domain of the Amyloid-β Peptide of Alzheimer’s Disease

2011 ◽  
Vol 50 (5) ◽  
pp. 1614-1618 ◽  
Author(s):  
Heather A. Feaga ◽  
Richard C. Maduka ◽  
Monique N. Foster ◽  
Veronika A. Szalai
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Binding Domain ◽  
Amyloid Β Peptide ◽  
Copper Binding

Evaluation of a Possible Role of Stigmatella aurantiaca ACE in Aβ Peptide Degradation: A Molecular Modeling Approach

2015 ◽  
Vol 25 (1) ◽  
pp. 26-36 ◽  
Author(s):  
Chidambar B. Jalkute ◽  
Kailas D. Sonawane
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Three Dimensional ◽  
Amyloid Β ◽  
Dynamics Simulation ◽  
Aβ Peptide ◽  
Three Dimensional Model ◽  
Aβ Peptides ◽  
Simulation Techniques ◽  
Stigmatella Aurantiaca

Amyloid-β (Aβ)-degrading enzymes are known to degrade Aβ peptides, a causative agent of Alzheimer's disease. These enzymes are responsible for maintaining Aβ concentration. However, loss of such enzymes or their Aβ-degrading activity because of certain genetic as well as nongenetic reasons initiates the accumulation of Aβ peptides in the human brain. Considering the limitations of the human enzymes in clearing Aβ peptide, the search for microbial enzymes that could cleave Aβ is necessary. Hence, we built a three-dimensional model of angiotensin-converting enzyme (ACE) from <i>Stigmatella aurantiaca</i> using homology modeling technique. Molecular docking and molecular dynamics simulation techniques were used to outline the possible cleavage mechanism of Aβ peptide. These findings suggest that catalytic residue Glu 434 of the model could play a crucial role to degrade Aβ peptide between Asp 7 and Ser 8. Thus, ACE from <i>S. aurantiaca</i> might cleave Aβ peptides similar to human ACE and could be used to design new therapeutic strategies against Alzheimer's disease.

Computational models explain how copper binding to amyloid-β peptide oligomers enhances oxidative pathways

2019 ◽  
Vol 21 (17) ◽  
pp. 8774-8784 ◽  
Author(s):  
Giovanni La Penna ◽  
Mai Suan Li
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Computational Models ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Copper Binding ◽  
Aβ Peptides ◽  
Intrinsically Disordered ◽  
Disordered Peptides

Amyloid-β (Aβ) peptides are intrinsically disordered peptides and their aggregation is the major hallmark of Alzheimer's disease (AD) development.

Characterization of copper binding to the peptide amyloid-β(1–16) associated with Alzheimer's disease

Biopolymers ◽  
2006 ◽  
Vol 83 (1) ◽  
pp. 20-31 ◽  
Author(s):  
Qing-Feng Ma ◽  
Jia Hu ◽  
Wei-Hui Wu ◽  
Hua-Dong Liu ◽  
Jin-Tang Du ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Copper Binding

scholarly journals Molecular Profiles of Amyloid-β Proteoforms in Typical and Rapidly Progressive Alzheimer’s Disease

2021 ◽  
Author(s):  
Aneeqa Noor ◽  
Saima Zafar ◽  
Mohsin Shafiq ◽  
Neelam Younas ◽  
Anna Siegert ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phenotypic Variability ◽  
Polyacrylamide Gel Electrophoresis ◽  
Amyloid Β ◽  
Rapid Progression ◽  
Aβ Peptide ◽  
Highly Hydrophobic

AbstractThe molecular determinants of atypical clinical variants of Alzheimer’s disease, including the recently discovered rapidly progressive Alzheimer’s disease (rpAD), are unknown to date. Fibrilization of the amyloid-β (Aβ) peptide is the most frequently studied candidate in this context. The Aβ peptide can exist as multiple proteoforms that vary in their post-translational processing, amyloidogenesis, and toxicity. The current study was designed to identify these variations in Alzheimer’s disease patients exhibiting classical (sAD) and rapid progression, with the primary aim of establishing if these variants may constitute strains that underlie the phenotypic variability of Alzheimer’s disease. We employed two-dimensional polyacrylamide gel electrophoresis and MALDI-ToF mass spectrometry to validate and identify the Aβ proteoforms extracted from targeted brain tissues. The biophysical analysis was conducted using RT-QuIC assay, confocal microscopy, and atomic force microscopy. Interactome analysis was performed by co-immunoprecipitation. We present a signature of 33 distinct pathophysiological proteoforms, including the commonly targeted Aβ40, Aβ42, Aβ4-42, Aβ11-42, and provide insight into their synthesis and quantities. Furthermore, we have validated the presence of highly hydrophobic Aβ seeds in rpAD brains that seeded reactions at a slower pace in comparison to typical Alzheimer’s disease. In vitro and in vivo analyses also verified variations in the molecular pathways modulated by brain-derived Aβ. These variations in the presence, synthesis, folding, and interactions of Aβ among sAD and rpAD brains constitute important points of intervention. Further validation of reported targets and mechanisms will aid in the diagnosis of and therapy for Alzheimer’s disease.

scholarly journals Down-regulation of cyclin D2 in amyloid β toxicity, inflammation, and Alzheimer’s disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259740
Author(s):  
Grzegorz A. Czapski ◽  
Magdalena Cieślik ◽  
Emilia Białopiotrowicz ◽  
Walter J. Lukiw ◽  
Joanna B. Strosznajder
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Cyclin Dependent Kinase ◽  
Wild Type ◽  
Cyclin D2 ◽  
Aβ Peptides ◽  
Expression Of Genes ◽  
Genes Encoding

In the current study, we analyzed the effects of the systemic inflammatory response (SIR) and amyloid β (Aβ) peptide on the expression of genes encoding cyclins and cyclin-dependent kinase (Cdk) in: (i) PC12 cells overexpressing human beta amyloid precursor protein (βAPP), wild-type (APPwt-PC12), or carrying the Swedish mutantion (APPsw-PC12); (ii) the murine hippocampus during SIR; and (iii) Alzheimer’s disease (AD) brain. In APPwt-PC12 expression of cyclin D2 (cD2) was exclusively reduced, and in APPsw-PC12 cyclins cD2 and also cA1 were down-regulated, but cA2, cB1, cB2, and cE1 were up-regulated. In the SIR cD2, cB2, cE1 were found to be significantly down-regulated and cD3, Cdk5, and Cdk7 were significantly up-regulated. Cyclin cD2 was also found to be down-regulated in AD neocortex and hippocampus. Our novel data indicate that Aβ peptide and inflammation both significantly decreased the expression of cD2, suggesting that Aβ peptides may also contribute to downregulation of cD2 in AD brain.

Synaptic Mitochondria: An Early Target of Amyloid-β and Tau in Alzheimer’s Disease

2021 ◽  
pp. 1-24
Author(s):  
Angie K. Torres ◽  
Claudia Jara ◽  
Han S. Park-Kang ◽  
Catalina M. Polanco ◽  
Diego Tapia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurofibrillary Tangles ◽  
Senile Plaques ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Predisposing Factor ◽  
Age Related ◽  
Synaptic Mitochondria

Alzheimer’s disease (AD) is characterized by cognitive impairment and the presence of neurofibrillary tangles and senile plaques in the brain. Neurofibrillary tangles are composed of hyperphosphorylated tau, while senile plaques are formed by amyloid-β (Aβ) peptide. The amyloid hypothesis proposes that Aβ accumulation is primarily responsible for the neurotoxicity in AD. Multiple Aβ-mediated toxicity mechanisms have been proposed including mitochondrial dysfunction. However, it is unclear if it precedes Aβ accumulation or if is a consequence of it. Aβ promotes mitochondrial failure. However, AβPP could be cleaved in the mitochondria producing Aβ peptide. Mitochondrial-produced Aβ could interact with newly formed ones or with Aβ that enter the mitochondria, which may induce its oligomerization and contribute to further mitochondrial alterations, resulting in a vicious cycle. Another explanation for AD is the tau hypothesis, in which modified tau trigger toxic effects in neurons. Tau induces mitochondrial dysfunction by indirect and apparently by direct mechanisms. In neurons mitochondria are classified as non-synaptic or synaptic according to their localization, where synaptic mitochondrial function is fundamental supporting neurotransmission and hippocampal memory formation. Here, we focus on synaptic mitochondria as a primary target for Aβ toxicity and/or formation, generating toxicity at the synapse and contributing to synaptic and memory impairment in AD. We also hypothesize that phospho-tau accumulates in mitochondria and triggers dysfunction. Finally, we discuss that synaptic mitochondrial dysfunction occur in aging and correlates with age-related memory loss. Therefore, synaptic mitochondrial dysfunction could be a predisposing factor for AD or an early marker of its onset.

scholarly journals NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer’s disease

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Xiao-fei He ◽  
Jing-hui Xu ◽  
Ge Li ◽  
Ming-yue Li ◽  
Li-li Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Aβ Peptide ◽  
Sporadic Alzheimer’S Disease ◽  
Potential Therapeutic Target ◽  
Nlrp3 Gene

Abstract Alzheimer’s disease (AD), the most common form of dementia, is marked by progressive cognitive decline, deposition of misfolded amyloid-β (Aβ) peptide and formation of neurofibrillary tangles. Recently, microglial training has emerged as an important contributor to neurological diseases, which augments the subsequent inflammation. However, how it affects the pathology of AD remains unknown. Here, using a mouse model of sporadic Alzheimer’s disease (SAD) induced by streptozotocin injection, we demonstrated that microglial training exacerbated Aβ accumulation, neuronal loss, and cognitive impairment. In addition, we injected MCC950 to inhibit NLRP3 activation and used an inducible Cre recombinase to delete the NLRP3 gene in microglia. Inhibition or depletion of microglial NLRP3 could protect against the pathologies of SAD and abolish the effects of microglial training. Our results identified microglial training as an important modifier of neuropathology in SAD and demonstrated that activation of NLRP3 inflammasome contributed to the pathologies and microglial training in SAD. Therefore, NLRP3 could be a potential therapeutic target for SAD treatment.

scholarly journals Effects of GrandFusion Diet on Cognitive Impairment in Transgenic Mouse Model of Alzheimer’s Disease

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 117 ◽  
Author(s):  
Jin Yu ◽  
Hong Zhu ◽  
Saeid Taheri ◽  
William Mondy ◽  
Stephen Perry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Cathepsin B ◽  
Memory Impairment ◽  
Chronic Traumatic Encephalopathy ◽  
Disease Process ◽  
Amyloid Β ◽  
Aβ Peptide ◽  
Model Of Alzheimer’S Disease

Alzheimer’s disease (AD) is the result of the deposition of amyloid β (Aβ) peptide into amyloid fibrils and tau into neurofibrillary tangles. At the present time, there are no possible treatments for the disease. We have recently shown that diets enriched in phytonutrients show protection or limit the extent of damage in a number of neurological disorders. GrandFusion (GF) diets have attenuated the outcomes in animal models of traumatic brain injury, cerebral ischemia, and chronic traumatic encephalopathy. In this study, we investigated the effect of GF diets in a mouse model of AD prior to the development of amyloid plaques to show how this treatment paradigm would alter the accumulation of Aβ peptide and related pathologic changes (i.e., inflammation, cathepsin B, and memory impairment). Administration of GF diets (2–4%) over a period of four months in APP/ΔPS1 double-transgenic mice resulted in attenuation in Aβ peptide levels, reduction of amyloid load, and inflammation, increased cathepsin B expression, and improved spatial orientation. Additionally, treatment with GF diets increased nerve growth factor (NGF) levels in the brain and tempered the memory impairment in the animal model. These data suggest that GF diets may alter the development and progression of the mechanisms associated with the disease process to effectively modify AD pathogenesis.

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