| Full text | |
| Author(s): |
Juvenal, Guilherme
;
Meinerz, Carine
;
Ayupe, Ana Carolina
;
Campos, Henrique Correia
;
Reis, Eduardo Moraes
;
Longo, Beatriz Monteiro
;
Pillat, Micheli Mainardi
;
Ulrich, Henning
Total Authors: 8
|
| Document type: | Journal article |
| Source: | CELL AND BIOSCIENCE; v. 14, n. 1, p. 19-pg., 2024-06-18. |
| Abstract | |
Background Neural progenitor cells (NPCs) can be cultivated from developing brains, reproducing many of the processes that occur during neural development. They can be isolated from a variety of animal models, such as transgenic mice carrying mutations in amyloid precursor protein (APP) and presenilin 1 and 2 (PSEN 1 and 2), characteristic of familial Alzheimer's disease (fAD). Modulating the development of these cells with inflammation-related peptides, such as bradykinin (BK) and its antagonist HOE-140, enables the understanding of the impact of such molecules in a relevant AD model. Results We performed a global gene expression analysis on transgenic neurospheres treated with BK and HOE-140. To validate the microarray data, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) was performed on 8 important genes related to the immune response in AD such as CCL12, CCL5, CCL3, C3, CX3CR1, TLR2 and TNF alpha and Iba-1. Furthermore, comparative analysis of the transcriptional profiles was performed between treatments, including gene ontology and reactome enrichment, construction and analysis of protein-protein interaction networks and, finally, comparison of our data with human dataset from AD patients. The treatments affected the expression levels of genes mainly related to microglia-mediated neuroinflammatory responses, with BK promoting an increase in the expression of genes that enrich processes, biological pathways, and cellular components related to immune dysfunction, neurodegeneration and cell cycle. B2 receptor inhibition by HOE-140 resulted in the reduction of AD-related anomalies caused in this system. Conclusions BK is an important immunomodulatory agent and enhances the immunological changes identified in transgenic neurospheres carrying the genetic load of AD. Bradykinin treatments modulate the expression rates of genes related to microglia-mediated neuroinflammation. Inhibiting bradykinin activity in Alzheimer's disease may slow disease progression. (AU) | |
| FAPESP's process: | 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases |
| Grantee: | Alexander Henning Ulrich |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 22/10950-5 - Selection and evaluation of proteins and fundamental mechanisms for the formation of long-term memory |
| Grantee: | Guilherme de Araujo Juvenal |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |