The salivary gland cells of Calliphora vomitoria larvae initiate and complete their own destruction in a programmed manner at the onset of metamorphosis. On entering the post-feeding period the larvae come to rest and the polytene salivary gland cells show a significant increase in DNA synthesis followed closely by a surge of mRNA synthesis accompanied by increasing protein production. During this prelude to cell death the new mRNA gives rise to at least 10 new proteins. The first new proteins having a MWt between 30 and 100kD appear by day 8 of the life-cycle and a number persist until the advent of cell death on day 9. Other new proteins appear in a cascade of production during day 8 and in vitro translation of mRNA produced at this time shows a new 55kD protein appearing before cell destruction. Significantly no evidence of DNA degeneration or laddering associated with classical apoptosis was observed, on the contrary considerable DNA synthesis in the form of chromosomal endoduplication or "genomic amplification" was seen; selective gene expression being apparently controlled at translational level. Overall the results strongly suggest a synthetically mediated programmed cell death in the metamorphosing salivary glands of the blow-fly which is distinct from apoptosis.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1006/cbir.1993.1002 | DOI Listing |
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 PDFAlzheimers Dement
December 2024
Virginia Commonwealth University, Richmond, VA, USA.
Background: Pyroptosis is a type of inflammasome-dependent cell death, in which gasdermin D (GSDMD) plays key roles as the executor. Neuroinflammation and pyroptosis have been indicated critical roles in neurodegenerative disorders including Alzheimer's disease (AD). Therefore, novel GSDMD inhibitors represent valuable probes to understand and validate GSDMD as a viable drug target for AD.
View Article and Find Full Text PDFBackground: There are no cures for Alzheimer's disease (AD), a progressive neurodegenerative disorder characterized by elevation of beta-amyloid and tau proteins besides neuronal death and causing cognitive impairment. Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways including those relevant to memory formation. PDE5 inhibition offers the potential to attenuate AD progression by acting at the downstream level of beta-amyloid and tau elevation.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Division of Neurodegenerative Disorders, St. Boniface Hospital Albrechtsen Research Centre, Winnipeg, MB, Canada.
Background: Alzheimer's disease (AD) is a neurodegenerative disorder primarily associated with aging, but manifests as a complex interplay of multiple factors. Decline in sex-hormones, particularly 17-beta estradiol, is linked to the aging process. The risk for onset of AD significantly increases with aging and loss of estradiol.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!