Reduced GLP-1R availability in the caudate nucleus with Alzheimer's disease.
| Autor: | Barrett, Emma, Ivey, Gabrielle, Cunningham, Adam, Coffman, Gary, Pemberton, Tyera, Chan Lee, Patra, Prabir, Day, James B., Lee, Peter H. U., Shim, Joon W. |
|---|---|
| Předmět: |
NUCLEOTIDE metabolism
GLUCAGON-like peptide-1 agonists ALZHEIMER'S disease RESEARCH funding DESCRIPTIVE statistics REVERSE transcriptase polymerase chain reaction CYTOSKELETAL proteins MESSENGER RNA GENE expression profiling ANIMAL experimentation CELL death CELL differentiation GENETIC mutation SEQUENCE analysis |
| Zdroj: | Frontiers in Aging Neuroscience; 2024, p1-11, 11p |
| Abstrakt: | The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer's disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD. [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
| Externí odkaz: |
|