Searching the Resource Information Network

Our searching services are busy right now. Please try again later

  • Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Alzheimer's-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets.

Meenakshisundaram Balasubramaniam | Akshatha Ganne | Nirjal Mainali | Sonu Pahal | Srinivas Ayyadevara | Robert J Shmookler Reis
iScience | 2024

Alzheimer's disease (AD) is characterized by peri-neuronal amyloid plaque and intra-neuronal neurofibrillary tangles. These aggregates are identified by the immunodetection of "seed" proteins (Aβ1-42 and hyperphosphorylated tau, respectively), but include many other proteins incorporated nonrandomly. Using click-chemistry intra-aggregate crosslinking, we previously modeled amyloid "contactomes" in SY5Y-APPSw neuroblastoma cells, revealing that aspirin impedes aggregate growth and complexity. By an analogous strategy, we now construct amyloid-specific aggregate interactomes of AD and age-matched-control hippocampi. Comparing these interactomes reveals AD-specific interactions, from which neural-network (NN) analyses predict proteins with the highest impact on pathogenic aggregate formation and/or stability. RNAi knockdowns of implicated proteins, in C. elegans and human-cell-culture models of AD, validated those predictions. Gene-Ontology meta-analysis of AD-enriched influential proteins highlighted the involvement of mitochondrial and cytoplasmic compartments in AD-specific aggregation. This approach derives dynamic consensus models of aggregate growth and architecture, implicating highly influential proteins as new targets to disrupt amyloid accrual in the AD brain.

Pubmed ID: 38274404

Associated grants

  • Agency: BLRD VA, United States
    Id: I01 BX001655
  • Agency: BLRD VA, United States
    Id: IK6 BX004851
  • Agency: NIA NIH HHS, United States
    Id: P01 AG012411
  • Agency: NIA NIH HHS, United States
    Id: R01 AG062254

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

View all literature mentions

Gephi (tool)

RRID:SCR_004293

Open-source software for network visualization and analysis helping data analysts to intuitively reveal patterns and trends, highlight outliers and tells stories with their data. It uses a 3D render engine to display large graphs in real-time and to speed up the exploration. Gephi combines built-in functionalities and flexible architecture to: explore, analyze, spatialize, filter, cluterize, manipulate and export all types of networks. Gephi runs on Windows, Linux and Mac OS X. Gephi is based on a visualize-and-manipulate paradigm which allow any user to discover networks and data properties. Moreover, it is designed to follow the chain of a case study, from data file to nice printable maps. It is open-source and free (GNU General Public License). Applications: * Exploratory Data Analysis: intuition-oriented analysis by networks manipulations in real time. * Link Analysis: revealing the underlying structures of associations between objects, in particular in scale-free networks. * Social Network Analysis: easy creation of social data connectors to map community organizations and small-world networks. * Biological Network analysis: representing patterns of biological data. * Poster creation: scientific work promotion with hi-quality printable maps. Gephi 0.7 architecture is modular and therefore allows developers to add and extend functionalities with ease. New features like Metrics, Layout, Filters, Data sources and more can be easily packaged in plugins and shared. The built-in Plugins Center automatically gets the list of plugins available from the Gephi Plugin portal and takes care of all software updates. Download, comment, and rate plugins provided by community members and third-party companies, or post your own contributions!

View all literature mentions

Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

View all literature mentions

Orange Data Mining (tool)

RRID:SCR_019811

Open source machine learning and data visualization. Data Mining Toolbox in Python used to build data analysis workflows visually, with large, diverse toolbox.

View all literature mentions

beta Amyloid antibody [DE2B4] (antibody)

RRID:AB_297770

This monoclonal targets beta Amyloid

View all literature mentions

Caenorhabditis Genetics Center (biomaterial supply resource)

RRID:SCR_007341

Center that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.

View all literature mentions