Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients
Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to cle...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Current Issues in Molecular Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1467-3045/47/6/392 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850156674070872064 |
|---|---|
| author | Benjamin Y. Klein Ofer N. Gofrit Charles L. Greenblatt |
| author_facet | Benjamin Y. Klein Ofer N. Gofrit Charles L. Greenblatt |
| author_sort | Benjamin Y. Klein |
| collection | DOAJ |
| description | Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., beta-amyloid) in AD brains and peripheral blood mononuclear cells (PBMCs) implicates BCG in upgrading the unfolded protein response (UPR). To test this hypothesis, pre- versus post-BCG PBMC proteins of the UPR pathway were compared in six NMIBC patients by capillary immunoelectrophoresis on an Abby instrument. PERK, the endoplasmic reticulum (ER) resident kinase, a stress-activated sensor, and its substrate alpha component of the eIF2 translation factor (eIF2a) complex inactivation were considered as potentially proapoptotic via a downstream proapoptotic transcription factor only if persistently high. GAPDH, a glycolytic marker of innate immunocyte training by BCG, and eight other UPR proteins were considered antiapoptotic. Summation of antiapoptotic %change scores per patient showed that the older the age, the lower the antiapoptotic %change. Higher antiapoptotic scores were observed upon a longer time from BCG treatment (with the exception of the patient in her ninth decade of life). Studies with more individuals could substantiate that BCG enhances the antiapoptotic aggregate-clearance effect of the UPR in PBMCs of NMIBC patients, which hypothetically protects brain cells against AD. |
| format | Article |
| id | doaj-art-9daef0d3c438491f8e1ac7872799cddc |
| institution | OA Journals |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Current Issues in Molecular Biology |
| spelling | doaj-art-9daef0d3c438491f8e1ac7872799cddc2025-08-20T02:24:25ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147639210.3390/cimb47060392Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer PatientsBenjamin Y. Klein0Ofer N. Gofrit1Charles L. Greenblatt2Department of Microbiology and Molecular Genetics, Hebrew University Medical School, Jerusalem 91120, IsraelDepartment of Urology, Hadassah University Medical School, Ein-Karem, Jerusalem 91120, IsraelDepartment of Microbiology and Molecular Genetics, Hebrew University Medical School, Jerusalem 91120, IsraelSeveral studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., beta-amyloid) in AD brains and peripheral blood mononuclear cells (PBMCs) implicates BCG in upgrading the unfolded protein response (UPR). To test this hypothesis, pre- versus post-BCG PBMC proteins of the UPR pathway were compared in six NMIBC patients by capillary immunoelectrophoresis on an Abby instrument. PERK, the endoplasmic reticulum (ER) resident kinase, a stress-activated sensor, and its substrate alpha component of the eIF2 translation factor (eIF2a) complex inactivation were considered as potentially proapoptotic via a downstream proapoptotic transcription factor only if persistently high. GAPDH, a glycolytic marker of innate immunocyte training by BCG, and eight other UPR proteins were considered antiapoptotic. Summation of antiapoptotic %change scores per patient showed that the older the age, the lower the antiapoptotic %change. Higher antiapoptotic scores were observed upon a longer time from BCG treatment (with the exception of the patient in her ninth decade of life). Studies with more individuals could substantiate that BCG enhances the antiapoptotic aggregate-clearance effect of the UPR in PBMCs of NMIBC patients, which hypothetically protects brain cells against AD.https://www.mdpi.com/1467-3045/47/6/392BCG vaccineperipheral blood mononuclear cellsunfolded protein responseendoplasmic reticulum stresscell signalingimmunoelectrophoretic |
| spellingShingle | Benjamin Y. Klein Ofer N. Gofrit Charles L. Greenblatt Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients Current Issues in Molecular Biology BCG vaccine peripheral blood mononuclear cells unfolded protein response endoplasmic reticulum stress cell signaling immunoelectrophoretic |
| title | Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients |
| title_full | Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients |
| title_fullStr | Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients |
| title_full_unstemmed | Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients |
| title_short | Testing Protein Stress Signals in Peripheral Immunocytes Under the Same Treatment Capable of Decreasing the Incidence of Alzheimer’s Disease in Bladder Cancer Patients |
| title_sort | testing protein stress signals in peripheral immunocytes under the same treatment capable of decreasing the incidence of alzheimer s disease in bladder cancer patients |
| topic | BCG vaccine peripheral blood mononuclear cells unfolded protein response endoplasmic reticulum stress cell signaling immunoelectrophoretic |
| url | https://www.mdpi.com/1467-3045/47/6/392 |
| work_keys_str_mv | AT benjaminyklein testingproteinstresssignalsinperipheralimmunocytesunderthesametreatmentcapableofdecreasingtheincidenceofalzheimersdiseaseinbladdercancerpatients AT oferngofrit testingproteinstresssignalsinperipheralimmunocytesunderthesametreatmentcapableofdecreasingtheincidenceofalzheimersdiseaseinbladdercancerpatients AT charleslgreenblatt testingproteinstresssignalsinperipheralimmunocytesunderthesametreatmentcapableofdecreasingtheincidenceofalzheimersdiseaseinbladdercancerpatients |