Identification of novel GDNF isoforms and cis-antisense GDNFOS gene and their regulation in human middle temporal gyrus of Alzheimer disease.
The study found that the mature GDNF peptide is down-regulated in Alzheimer disease patients, while a specific GDNF isoform is up-regulated, suggesting potential dysregulation in neurodegenerative conditions.
Where it sits
this study against the rest of the dnsp-11 (dopamine neuron stimulating peptide-11) corpusSummary and findings
This study investigated the expression of GDNF isoforms and the novel GDNFOS gene in the middle temporal gyrus of Alzheimer disease (AD) and Huntington disease (HD) patients compared to normal controls. It was found that the mature GDNF peptide was down-regulated in AD patients, while the transcript of GDNF isoform from human exon 2 was up-regulated. No treatment claims are made.
Abstract
Primate-specific genes and isoforms could provide insight into human brain diseases. Our bioinformatic analysis revealed that there are possibly five isoforms of human GDNF gene with different pre- and pro-regions by inter- and intra-exon splicing. By using TaqMan primer probe sets, designed between exons, we verified the expression of all isoforms. Furthermore, a novel GDNFOS gene was found to be transcribed from the opposite strand of GDNF gene. GDNFOS gene has four exons that are spliced into different isoforms. GDNFOS1 and GDNFOS2 are long noncoding RNAs, and GDNFOS3 encodes a protein of 105 amino acids. To study human GDNF and GDNFOS regulation in neurodegenerative diseases, the protein and mRNA levels were measured by Western blot and RT-quantitative PCR, respectively, in postmortem middle temporal gyrus (MTG) of Alzheimer disease (AD) and Huntington disease (HD) patients in comparison with those of normal controls. In the MTG of AD patients, the mature GDNF peptide was down-regulated; however, the transcript of GDNF isoform from human exon 2 was up-regulated, whereas that of the conserved isoform from exon 1 remained unchanged in comparison with those of normal controls. In contrast, the mature GDNF peptide and the isoform mRNA levels were not changed in the MTG of HD. The findings of novel GDNF and GDNFOS isoforms and differences in tissue expression patterns dysregulated in AD brains may further reveal the role of endogenous GDNF in human brain diseases.
Background
The paper addresses the role of GDNF (Glial cell line-derived neurotrophic factor) isoforms and their regulation in Alzheimer's disease, a condition characterized by neurodegeneration. Prior research has indicated that GDNF may play a role in neuronal survival and function, but the specific isoforms and regulatory mechanisms remain poorly understood. This study aims to elucidate these aspects in the context of Alzheimer's pathology.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Key findings
- Not reported in abstract.
Limitations
- Not reported in abstract.