RESUMEN
Lung cancer is a severe and the leading cause of cancer related deaths in men and women all over the world. Tumor suppressor protein (TP53) encoded by the TP53 gene which plays a pivotal role in various cellular tumor suppression processes viz cell cycle arrest and apoptosis. Henceforth, the present study was aimed to TP53 exon4 variants from lung carcinoma. Histopathologic and clinically proven 20 patients of lung cancer were enrolled in this study the average age of patients was 45 ± 8 years which categorized as early onset of lung cancer. Genomic DNA was isolated from the blood specimen of patients. Extracted DNA was subjected to PCR amplification for exon 4 of TP53 using appropriate primers and subsequently amplified products were applied to nucleotide alterations via using the DNA sanger sequencing. The genetic analysis documented five variants in exon4 of TP53 which include viz. 4 substitutions [c.215 > C at codon 72, C. 358-359AA > GG at codon 120] were highly prevalent, occurring in 63% and 25% frequency in patients. Other two variants viz. C. 358 A > C at codon 120, C. 365T > G at codon 122 were present at frequency of 15% whilst one deletion variant [152 del C] was found with 5% frequency. Furthermore, alterations on codon 72, 120,122 and 51 were characterized as possibly damaging by Poly Phen-2 and decreased stability using stability bioinformatic tool. Taken together all these findings infer that TP53 gene involved in modulation and susceptibility to lung cancer.
RESUMEN
Regulated cell death (RCD) is an ordered and tightly orchestrated set of changes/signaling events in both gene expression and protein activity and is responsible for normal development as well as maintenance of tissue homeostasis. Aberrant activation of this pathway results in cell death by various mechanisms including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy-dependent cell death. Such pathological changes in neurons alone or in combination have been observed in the pathogenesis of various neurodegenerative diseases including Alzheimer's disease (AD). Pathological hallmarks of AD focus primarily on the accumulation of two main protein markers: amyloid ß peptides and abnormally phosphorylated tau proteins. These protein aggregates result in the formation of A-ß plaques and neuro-fibrillary tangles (NFTs) and induce neuroinflammation and neurodegeneration over years to decades leading to a multitude of cognitive and behavioral deficits. Autopsy findings of AD reveal massive neuronal death manifested in the form of cortical volume shrinkage, reduction in sizes of gyri to up to 50% and an increase in the sizes of sulci. Multiple forms of cell death have been recorded in neurons from different studies conducted so far. However, understanding the mechanism/s of neuronal cell death in AD patients remains a mystery as the trigger that results in aberrant activation of RCD is unknown and because of the limited availability of dying neurons. This review attempts to elucidate the process of Regulated cell death, how it gets unregulated in response to different intra and extracellular stressors, various forms of unregulated cell death, their interplay and their role in pathogenesis of Alzheimer's Disease in both human and experimental models of AD. Further we plan to explore the correlation of both amyloid-beta and Tau with neuronal loss as seen in AD.
