Title :

Cxcr4 involvement in neurodegenerative diseases

Author(s) :

Bonham, Luke W. [Auteur]
Karch, Celeste M. [Auteur]
Fan, Chun C. [Auteur]
Tan, Chin [Auteur]
Geier, Ethan G. [Auteur]
Wang, Yunpeng [Auteur]
Wen, Natalie L. [Auteur]
Broce, Iris J. [Auteur]
Li, Yi [Auteur]
Barkovich, Matthew J. [Auteur]
Ferrari, Raffaele [Auteur]
Hardy, John [Auteur]
Momeni, Parastoo [Auteur]
Hoglinger, Gunter U. [Auteur]
Muller, Ulrich [Auteur]
Hess, Christopher P. [Auteur]
Sugrue, Leo P. [Auteur]
Dillon, William P. [Auteur]
Schellenberg, Gerard D. [Auteur]
Miller, Bruce L. [Auteur]
Andreassen, Ole A. [Auteur]
Dale, Anders M. [Auteur]
Barkovich, A James [Auteur]
Yokoyama, Jennifer S. [Auteur]
Desikan, Rahul S. [Auteur]

Journal title :

Translational psychiatry

Abbreviated title :

Transl Psychiatry

Volume number :

8

Pages :

73

Publication date :

2018-04-11

ISSN :

2158-3188

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared ...
Show more >Neurodegenerative diseases likely share common underlying pathobiology. Although prior work has identified susceptibility loci associated with various dementias, few, if any, studies have systematically evaluated shared genetic risk across several neurodegenerative diseases. Using genome-wide association data from large studies (total n = 82,337 cases and controls), we utilized a previously validated approach to identify genetic overlap and reveal common pathways between progressive supranuclear palsy (PSP), frontotemporal dementia (FTD), Parkinson's disease (PD) and Alzheimer's disease (AD). In addition to the MAPT H1 haplotype, we identified a variant near the chemokine receptor CXCR4 that was jointly associated with increased risk for PSP and PD. Using bioinformatics tools, we found strong physical interactions between CXCR4 and four microglia related genes, namely CXCL12, TLR2, RALB, and CCR5. Evaluating gene expression from post-mortem brain tissue, we found that expression of CXCR4 and microglial genes functionally related to CXCR4 was dysregulated across a number of neurodegenerative diseases. Furthermore, in a mouse model of tauopathy, expression of CXCR4 and functionally associated genes was significantly altered in regions of the mouse brain that accumulate neurofibrillary tangles most robustly. Beyond MAPT, we show dysregulation of CXCR4 expression in PSP, PD, and FTD brains, and mouse models of tau pathology. Our multi-modal findings suggest that abnormal signaling across a 'network' of microglial genes may contribute to neurodegeneration and may have potential implications for clinical trials targeting immune dysfunction in patients with neurodegenerative diseases.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Research team(s) :

Troubles cognitifs dégénératifs et vasculaires

Submission date :

2019-11-27T14:30:51Z