Quantitative and qualitative control of oral bacterial flora is a major issue in oral pathology and in the prophylaxis against cavities. Recent findings suggest that it is possible to induce local immune responses delivering antigens on palatine tonsils. M cells play an important role in the start of the immune response. These cells are located in the epithelia overlaying mucosal lymphoid follicles and are responsible for the uptake of particulate antigens. The identification of reliable markers for M cell is therefore extremely important. Since it has been reported that tonsillar immunization leads to the secretion of high levels of specific salivary antibody, we undertook a study to identify a marker for tonsillar M cells in order to plan strategies of oral immunization against oral pathogens. We studied cytokeratin 20 expression in rabbit tonsils by immunofluorescence and confocal microscopy. Cytokeratin 20 immunoreactive cells were observed in all samples examined. These cells were identified as M cells as they co-expressed vimentin, a well-known marker of rabbit M cells, and they actively uptook particulate material. It is therefore possible to hypothesize the use of tonsil M cells as a possible site for antigen delivery of particle-based vaccines against oral pathogens.
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Background: The autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) are key proteostasis mechanisms in cells, which are dysfunctional in AD and linked to protein aggregation and neuronal death. Autophagy is over activated in Alzheimer's disease brain whereas UPS is severely impaired. Activating autophagy has received most attention, however recent evidence suggests that UPS can clear aggregate proteins and a potential therapeutic target for AD and protein misfolding diseases.
View Article and Find Full Text PDFBackground: Alzheimer's disease (AD) is the most common cause of dementia worldwide. It is characterized by dysfunction in the U1 small nuclear ribonucleoproteins (snRNPs) complex, which may precede TAU aggregation, enhancing premature polyadenylation, spliceosome dysfunction, and causing cell cycle reentry and death. Thus, we evaluated the effects of a synthetic single-stranded cDNA, called APT20TTMG, in induced pluripotent stem cells (iPSC) derived neurons from healthy and AD donors and in the Senescence Accelerated Mouse-Prone 8 (SAMP8) model.
View Article and Find Full Text PDFBackground: Immunotherapy of Alzheimer's disease (AD) is a promising approach to reducing the accumulation of beta-amyloid, a critical event in the onset of the disease. Targeting the group II metabotropic glutamate receptors, mGluR2 and mGluR3, could be important in controlling Aβ production, although their respective contribution remains unclear due to the lack of selective tools.
Method: 5xFAD mice were chronically treated by a brain penetrant camelid single domain antibody (VHH or nanobody) that is an activator of mGluR2.
Alzheimers Dement
December 2024
Columbia University Irving Medical Center, New York, NY, USA.
Background: Genetic studies indicate a causal role for microglia, the innate immune cells of the central nervous system (CNS), in Alzheimer's disease (AD). Despite the progress made in identifying genetic risk factors, such as CD33, and underlying molecular changes, there are currently limited treatment options for AD. Based on the immune-inhibitory function of CD33, we hypothesize that inhibition of CD33 activation may reverse microglial suppression and restore their ability to resolve inflammatory processes and mitigate pathogenic amyloid plaques, which may be neuroprotective.
View Article and Find Full Text PDFBackground: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
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