scholarly journals High Throughput Screening at the Membrane Interface Reveals New Inhibitors of Amyloid-β

2019 ◽  
Author(s):  
Sarah J. Cox ◽  
Brian Lam ◽  
Ajay Prasad ◽  
Hannah A. Marietta ◽  
Nicholas V. Stander ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Membrane ◽  
Small Molecules ◽  
High Throughput ◽  
High Throughput Screening ◽  
Amyloid Β ◽  
Amyloid Aggregation ◽  
Membrane Interface

Amyloid-β aggregation at the cell-membrane of neruonal cells is implicated as a source of toxicity for Alzheimer’s disease. Small molecules have been studied for their ability to supress amyloid aggregation and toxicity, but the presence of membranes negate their activity. Here, we have identified 5 small molecules that are active at the membrane interface.

scholarly journals Link between Diabetes and Alzheimer’s Disease Due to the Shared Amyloid Aggregation and Deposition Involving Both Neurodegenerative Changes and Neurovascular Damages

2020 ◽  
Vol 9 (6) ◽  
pp. 1713 ◽  
Author(s):  
Gabriela Dumitrita Stanciu ◽  
Veronica Bild ◽  
Daniela Carmen Ababei ◽  
Razvan Nicolae Rusu ◽  
Alina Cobzaru ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Social Impact ◽  
Significant Risk ◽  
Amyloid Β ◽  
Detailed Knowledge ◽  
Amyloid Aggregation ◽  
Islet Amyloid ◽  
Type 3 ◽  
Insight Into

Diabetes and Alzheimer’s disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms “diabetes type 3” or “brain diabetes” have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer’s disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

[P3-245]: ANALYSIS OF THE HUMORAL RESPONSE IN ALZHEIMER's DISEASE USING THE HIGH-THROUGHPUT SCREENING COMBINATION OF T7 PHAGE LIBRARIES AND PROTEIN MICROARRAYS

2017 ◽  
Vol 13 (7S_Part_21) ◽  
pp. P1034-P1034
Author(s):  
Pablo San Segundo-Acosta ◽  
Ana Montero-Calle ◽  
Maria Garranzo-Asensio ◽  
Carmen Oeo-Santos ◽  
Juan Carlos López-Rodríguez ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
High Throughput Screening ◽  
Humoral Response ◽  
Protein Microarrays ◽  
Phage Libraries ◽  
T7 Phage

Phosphorylation of a full length amyloid-β peptide modulates its amyloid aggregation, cell binding and neurotoxic properties

2017 ◽  
Vol 13 (8) ◽  
pp. 1545-1551 ◽  
Author(s):  
Elaheh Jamasbi ◽  
Frances Separovic ◽  
Mohammed Akhter Hossain ◽  
Giuseppe Donato Ciccotosto
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Β ◽  
Amyloid Plaques ◽  
Full Length ◽  
Amyloid Β Peptide ◽  
Amyloid Aggregation ◽  
Cell Binding ◽  
The Brain

Phosphorylation of Aβ42 promotes the formation of amyloid plaques in the brain, which lack the neurotoxic properties associated with oligomeric species causing pathogenesis in Alzheimer's disease.

An integrated strategy for rapid screening of multi-target lead compounds for the treatment of Alzheimer's disease from traditional Chinese medicines by UHPLC combined with high-throughput screening: A case study on Salviae Miltiorrhizae Radix et Rhizoma

2021 ◽  
Vol 17 ◽  
Author(s):  
Minmin Zhang ◽  
Siduo Zhou ◽  
Wei Liu ◽  
Huijiao Yan ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Throughput ◽  
Inhibitory Activity ◽  
High Throughput Screening ◽  
Hplc Analysis ◽  
Salviae Miltiorrhizae ◽  
Salviae Miltiorrhizae Radix ◽  
Ache Inhibitory Activity

Background: Salviae Miltiorrhizae Radix et Rhizoma (Red Sage root) is widely used in traditional Chinese medicine (TCM) for the treatment of Alzheimer’s disease (AD) with demonstrated curative effects, based on the concept of "one drug with multiple therapeutic targets," which appears to be a good strategy for AD treatment. Objective: This study aimed to develop of high-throughput screening (HTS) method for multi-therapeutic target components found in complex TCMs, which are active against AD, using Red Sage root as the case study. Method: Acetylcholinesterase (AChE) inhibitors (AChEIs) from Red Sage root extracts were pre-screened by ultrafiltration-HPLC (UF-HPLC) analysis, in which AChE was added to the extract and then ultrafiltered to remove non-binding compounds. Potential AChEIs were identified by HPLC analysis of compounds bound to AChE. A microplate-based HTS was then used to quantify the AChE inhibitory activity and antioxidant activity of the pre-screened compounds. Results: Pre-screening found ten potential inhibitors, which were identified by ESI-TOF/MS; six of these were purified by semi-preparative HPLC: Oleoyl neocryptotanshinone (1), Dihydrotanshinone Ⅰ (2), Cryptotanshinone (3), Tanshinone Ⅰ (4), Tanshinone ⅡA (5) and Miltirone (6). All six compounds had good AChE inhibitory activity and weak DPPH scavenging capacity. Conclusion: This study provides a platform and technology support for the rapid discovery of multi-target components, potentially active against AD, from complex TCMs and with strong potential for adaptation to the discovery of treatments for other diseases.

Different Fates of Alzheimer’s Disease Amyloid-β Fibrils Remodeled by Biocompatible Small Molecules

2012 ◽  
Vol 14 (1) ◽  
pp. 264-274 ◽  
Author(s):  
Jacob A. Irwin ◽  
H. Edward Wong ◽  
Inchan Kwon
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Amyloid Β

scholarly journals Modulatory Effects of Autophagy on APP Processing as a Potential Treatment Target for Alzheimer’s Disease

Biomedicines ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 5
Author(s):  
Md. Ataur Rahman ◽  
Md Saidur Rahman ◽  
MD. Hasanur Rahman ◽  
Mohammad Rasheduzzaman ◽  
ANM Mamun-Or-Rashid ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Small Molecules ◽  
Early Stage ◽  
Pathological Condition ◽  
Critical Role ◽  
Amyloid Β ◽  
Treatment Target ◽  
App Processing ◽  
Phosphorylated Tau Protein

Alzheimer’s disease (AD) is characterized by the formation of intracellular aggregate composed of heavily phosphorylated tau protein and extracellular deposit of amyloid-β (Aβ) plaques derived from proteolysis cleavage of amyloid precursor protein (APP). Autophagy refers to the lysosomal-mediated degradation of cytoplasmic constituents, which plays a critical role in maintaining cellular homeostasis. Importantly, recent studies reported that dysregulation of autophagy is associated in the pathogenesis of AD, and therefore, autophagy modulation has gained attention as a promising approach to treat AD pathogenesis. In AD, both the maturation of autolysosomes and its retrograde transports have been obstructed, which causes the accumulation of autophagic vacuoles and eventually leads to degenerating and dystrophic neurites function. However, the mechanism of autophagy modulation in APP processing and its pathogenesis have not yet been fully elucidated in AD. In the early stage of AD, APP processing and Aβ accumulation-mediated autophagy facilitate the removal of toxic protein aggregates via mTOR-dependent and -independent pathways. In addition, a number of autophagy-related genes (Atg) and APP are thought to influence the development of AD, providing a bidirectional link between autophagy and AD pathology. In this review, we summarized the current observations related to autophagy regulation and APP processing in AD, focusing on their modulation associated with the AD progression. Moreover, we emphasizes the application of small molecules and natural compounds to modulate autophagy for the removal and clearance of APP and Aβ deposits in the pathological condition of AD.

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