BackgroundThe AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD.MethodsPUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer’s disease. This research explores inverse relationship between AD and cancer, also investigates other factors behind AD using several already published research literature to find the etiology of AD.ResultsCancer and Alzheimer’s disease have inverse relationship in many aspects such as P53, estrogen, neurotrophins and growth factors, growth and proliferation, cAMP, EGFR, Bcl-2, apoptosis pathways, IGF-1, HSV, TDP-43, APOE variants, notch signals and presenilins, NCAM, TNF alpha, PI3K/AKT/MTOR pathway, telomerase, ROS, ACE levels. AD occurs when brain neurons have weakened growth, cell survival responses, maintenance mechanisms, weakened anti-stress responses such as Vimentin, Carbonic anhydrases, HSPs, SAPK. In cancer, these responses are upregulated and maintained. Evolutionarily conserved responses and maintenance mechanisms such as FOXO are impaired in AD.Countermeasures or compensatory mechanisms by AD affected neurons such as Tau, Beta Amyloid, S100, are last attempts for survival which may be protective for certain time, or can speed up AD in Alzheimer’s microenvironment via C-ABL activation, GSK3, neuro-inflammation.ConclusionsAlzheimer’s disease and Cancer have inverse relationship; many factors that are upregulated in any cancer to sustain growth and survival are downregulated in Alzheimer’s disease contributing to neuro-degeneration. When aged neurons or genetically susceptible neurons have weakened growth, cell survival and anti-stress responses, age related gene expression changes, altered regulation of cell death and maintenance mechanisms, they contribute to Alzheimer’s disease. Countermeasures by AD neurons such as Beta Amyloid Plaques, NFTs, S100, are last attempts for survival and this provides neuroprotection for certain time and ultimately may become pathological and speed up AD. This study may contribute in developing new potential diagnostic tests, interventions and treatments.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0765-2) contains supplementary material, which is available to authorized users.

Background Onset, development and progression of atherosclerosis are complex multistep processes. Many aspects of atherogenesis are not yet properly known. This study investigates the changes in vasculature that contribute to switching of vascular cells towards atherogenesis, focusing mainly on ageing. Methods Databases including PubMed, MEDLINE and Google Scholar were searched for published articles without any date restrictions, involving atherogenesis, vascular homeostasis, aging, gene expression, signaling pathways, angiogenesis, vascular development, vascular cell differentiation and maintenance, vascular stem cells, endothelial and vascular smooth muscle cells. Results Atherogenesis is a complex multistep process that unfolds in a sequence. It is caused by alterations in: epigenetics and genetics, signaling pathways, cell circuitry, genome stability, heterotypic interactions between multiple cell types and pathologic alterations in vascular microenvironment. Such alterations involve pathological changes in: Shh, Wnt, NOTCH signaling pathways, TGF beta, VEGF, FGF, IGF 1, HGF, AKT/PI3K/ mTOR pathways, EGF, FOXO, CREB, PTEN, several apoptotic pathways, ET – 1, NF-κB, TNF alpha, angiopoietin, EGFR, Bcl − 2, NGF, BDNF, neurotrophins, growth factors, several signaling proteins, MAPK, IFN, TFs, NOs, serum cholesterol, LDL, ephrin, its receptor pathway, HoxA5, Klf3, Klf4, BMPs, TGFs and others. This disruption in vascular homeostasis at cellular, genetic and epigenetic level is involved in switching of the vascular cells towards atherogenesis. All these factors working in pathologic manner, contribute to the development and progression of atherosclerosis. Conclusion The development of atherosclerosis involves the switching of gene expression towards pro-atherogenic genes. This happens because of pathologic alterations in vascular homeostasis. When pathologic alterations in epigenetics, genetics, regulatory genes, microenvironment and vascular cell biology accumulate beyond a specific threshold, then the disease begins to express itself phenotypically. The process of biological ageing is one of the most significant factors in this aspect as it is also involved in the decline in homeostasis, maintenance and integrity. The process of atherogenesis unfolds sequentially (step by step) in an interconnected loop of pathologic changes in vascular biology. Such changes are involved in ‘switching’ of vascular cells towards atherosclerosis.

Background Glioblastoma is one of the most aggressive tumors. The etiology and the factors determining its onset are not yet entirely known. This study investigates the origins of GBM, and for this purpose, it focuses primarily on developmental gliogenic processes. It also focuses on the impact of the related neurogenic developmental processes in glioblastoma oncogenesis. It also addresses why glial cells are at more risk of tumor development compared to neurons. Methods Databases including PubMed, MEDLINE, and Google Scholar were searched for published articles without any date restrictions, involving glioblastoma, gliogenesis, neurogenesis, stemness, neural stem cells, gliogenic signaling and pathways, neurogenic signaling and pathways, and astrocytogenic genes. Results The origin of GBM is dependent on dysregulation in multiple genes and pathways that accumulatively converge the cells towards oncogenesis. There are multiple layers of steps in glioblastoma oncogenesis including the failure of cell fate-specific genes to keep the cells differentiated in their specific cell types such as p300, BMP, HOPX, and NRSF/REST. There are genes and signaling pathways that are involved in differentiation and also contribute to GBM such as FGFR3, JAK-STAT, and hey1. The genes that contribute to differentiation processes but also contribute to stemness in GBM include notch, Sox9, Sox4, c-myc gene overrides p300, and then GFAP, leading to upregulation of nestin, SHH, NF-κB, and others. GBM mutations pathologically impact the cell circuitry such as the interaction between Sox2 and JAK-STAT pathway, resulting in GBM development and progression. Conclusion Glioblastoma originates when the gene expression of key gliogenic genes and signaling pathways become dysregulated. This study identifies key gliogenic genes having the ability to control oncogenesis in glioblastoma cells, including p300, BMP, PAX6, HOPX, NRSF/REST, LIF, and TGF beta. It also identifies key neurogenic genes having the ability to control oncogenesis including PAX6, neurogenins including Ngn1, NeuroD1, NeuroD4, Numb, NKX6-1 Ebf, Myt1, and ASCL1. This study also postulates how aging contributes to the onset of glioblastoma by dysregulating the gene expression of NF-κB, REST/NRSF, ERK, AKT, EGFR, and others.