Neuroimmune dysfunction in frontotemporal dementia: Insights from progranulin and C9orf72 deficiency |
| |
Affiliation: | 1. Department of Pathology, University of California San Francisco, San Francisco, CA, 94143, USA;2. Biomedical Sciences (BMS) Graduate Program, University of California San Francisco, San Francisco, CA, 94143, USA;3. Department of Neurology, Memory and Aging Center, University of California San Francisco, San Francisco, CA, 94158, USA;4. Pathology Service 113B, San Francisco VA Health Care Systems, San Francisco, CA, 94121, USA |
| |
Abstract: | Neuroimmune dysfunction is a cardinal feature of neurodegenerative diseases. But how immune dysregulation in the brain and peripheral organs contribute to neurodegeneration remains unclear. Here, we discuss the recent advances highlighting neuroimmune dysfunction as a key disease-driving factor in frontotemporal dementia (FTD). We provide an overview of the clinical observations supporting a high prevalence of autoimmune diseases in FTD patients with mutations in GRN or C9orf72. We then focus on a myriad of evidence from human genetic studies, mouse models, in vitro assays, and multi-omics platform, which indicate that haploinsufficiency in GRN and C9orf72 promotes neuroimmune dysfunction and contributes to neurodegeneration and premature death. These compelling data provide key insights to disease mechanisms, biomarker discovery, and therapeutic interventions for FTD (120 words). |
| |
Keywords: | FTD" },{" #name" :" keyword" ," $" :{" id" :" pc_ZusEaoDRXz" }," $$" :[{" #name" :" text" ," _" :" Frontotemporal dementia FTLD" },{" #name" :" keyword" ," $" :{" id" :" pc_2ns328BhqN" }," $$" :[{" #name" :" text" ," _" :" Frontotemporal lobar degeneration AD" },{" #name" :" keyword" ," $" :{" id" :" pc_LJF5dvKBM5" }," $$" :[{" #name" :" text" ," _" :" Alzheimer's disease GWAS" },{" #name" :" keyword" ," $" :{" id" :" pc_eklOzJpUUz" }," $$" :[{" #name" :" text" ," _" :" Genome-wide association studies TDP-43" },{" #name" :" keyword" ," $" :{" id" :" pc_zAjLVW3rbg" }," $$" :[{" #name" :" text" ," _" :" TAR DNA binding protein 43 FUS" },{" #name" :" keyword" ," $" :{" id" :" pc_UjjLc2y3Hb" }," $$" :[{" #name" :" text" ," _" :" Fused in sarcoma RA" },{" #name" :" keyword" ," $" :{" id" :" pc_qaAzIpu6iy" }," $$" :[{" #name" :" text" ," _" :" Rheumatoid arthritis SLE" },{" #name" :" keyword" ," $" :{" id" :" pc_2Siz31DKMl" }," $$" :[{" #name" :" text" ," _" :" Systemic lupus erythematosus M6PR" },{" #name" :" keyword" ," $" :{" id" :" pc_ykTm316KME" }," $$" :[{" #name" :" text" ," _" :" Mannose 6-phosphate receptor LRP1" },{" #name" :" keyword" ," $" :{" id" :" pc_VdDxygD3xw" }," $$" :[{" #name" :" text" ," _" :" Low-density lipoprotein receptor-related protein 1 TNF" },{" #name" :" keyword" ," $" :{" id" :" pc_mwFUidCXDy" }," $$" :[{" #name" :" text" ," _" :" Tumor necrosis factor TNFR" },{" #name" :" keyword" ," $" :{" id" :" pc_MYpDQZic8U" }," $$" :[{" #name" :" text" ," _" :" Tumor necrosis factor receptor SNP" },{" #name" :" keyword" ," $" :{" id" :" pc_CxeMG1cSk1" }," $$" :[{" #name" :" text" ," _" :" Single nucleotide polymorphism NCL" },{" #name" :" keyword" ," $" :{" id" :" pc_Z1wFQJ3nhe" }," $$" :[{" #name" :" text" ," _" :" Neuronal ceroid lipofuscinosis NPC" },{" #name" :" keyword" ," $" :{" id" :" pc_yA8EmEz31t" }," $$" :[{" #name" :" text" ," _" :" Niemann-Pick's disease MPS" },{" #name" :" keyword" ," $" :{" id" :" pc_5m8mzwnbYy" }," $$" :[{" #name" :" text" ," _" :" Mucopolysaccharidosis BBB" },{" #name" :" keyword" ," $" :{" id" :" pc_9K5M8873xP" }," $$" :[{" #name" :" text" ," _" :" Blood-brain barrier ALS" },{" #name" :" keyword" ," $" :{" id" :" pc_t0Dm7cv754" }," $$" :[{" #name" :" text" ," _" :" Amyotrophic lateral sclerosis PGRN" },{" #name" :" keyword" ," $" :{" id" :" pc_LI2qNZZg2m" }," $$" :[{" #name" :" text" ," _" :" Progranulin (protein) PSAP" },{" #name" :" keyword" ," $" :{" id" :" pc_rUALAJYjwF" }," $$" :[{" #name" :" text" ," _" :" Prosaposin (protein) C9orf72" },{" #name" :" keyword" ," $" :{" id" :" pc_6OAwqm7973" }," $$" :[{" #name" :" text" ," _" :" Chromosome 9 open reading frame 72 OCD" },{" #name" :" keyword" ," $" :{" id" :" pc_eHREjY2P1n" }," $$" :[{" #name" :" text" ," _" :" Obsessive-compulsive disorder |
本文献已被 ScienceDirect 等数据库收录! |
|