Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Evidence of Trem2 variant associated with triple risk of alzheimer's disease
PLoS ONE, Volume 9, No. 3, Article e92648, Year 2014
Notification
URL copied to clipboard!
Description
Alzheimer's disease is one of the main causes of dementia among elderly individuals and leads to the neurodegeneration of different areas of the brain, resulting in memory impairments and loss of cognitive functions. Recently, a rare variant that is associated with 3-fold higher risk of Alzheimer's disease onset has been found. The rare variant discovered is a missense mutation in the loop region of exon 2 of Trem2 (rs75932628-T, Arg47His). The aim of this study was to investigate the evidence for potential structural and functional significance of Trem2 gene variant (Arg47His) through molecular dynamics simulations. Our results showed the alteration caused due to the variant in TREM2 protein has significant effect on the ligand binding affinity as well as structural configuration. Based on molecular dynamics (MD) simulation under salvation, the results confirmed that native form of the variant (Arg47His) might be responsible for improved compactness, hence thereby improved protein folding. Protein simulation was carried out at different temperatures. At 300K, the deviation of the theoretical model of TREM2 protein increased from 2.0 Å at 10 ns. In contrast, the deviation of the Arg47His mutation was maintained at 1.2 Å until the end of the simulation (t = 10 ns), which indicated that Arg47His had reached its folded state. The mutant residue was a highly conserved region and was similar to "immunoglobulin V-set" and "immunoglobulin-like folds". Taken together, the result from this study provides a biophysical insight on how the studied variant could contribute to the genetic susceptibility to Alzheimer's disease. © 2014 Abduljaleel et al.
Authors & Co-Authors
Abduljaleel, Zainularifeen A.
Saudi Arabia, Makkah
Umm Al-qura University
Saudi Arabia, Riyadh
College of Sciences
Al-Allaf, Faisal Ahmad
Saudi Arabia, Makkah
Umm Al-qura University
Khan, Wajahatullah M.
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Athar, Mohammad
Saudi Arabia, Makkah
Umm Al-qura University
Shahzad, Naiyer
Saudi Arabia, Makkah
Umm Al-qura University
Taher, Mohiuddin M.
Saudi Arabia, Makkah
Umm Al-qura University
Elrobh, Mohamed
Saudi Arabia, Riyadh
College of Sciences
Alanazi, Mohammad Saud
Saudi Arabia, Riyadh
College of Sciences
El-Huneidi, Waseem
Saudi Arabia, Riyadh
King Saud Bin Abdulaziz University for Health Sciences
Statistics
Citations: 41
Authors: 9
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0092648
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Mental Health