Identification of biomarkers and pathways to identify novel therapeutic targets in Alzheimer’s disease: Insights from a systems biomedicine perspective

Rahman, Rezanur; Islam, Tania; Zaman, Toyfiquz; Shahjaman, Md.; Karim, Md. Rezaul; Huq, Fazlul; Quinn, Julian M.W.; Holsinger, R. M. Damian; Moni, Mohammad Ali

doi:10.1101/481879

Cited by 8 publications

(9 citation statements)

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“…In the present work, we studied gene expression data of AD and IS patients in order to identify genes dysregulated in both diseases that may be candidate disease biomarkers and potential therapeutic targets. The candidate biomarker genes were explored in microarray and RNA-seq studies of AD and IS, an approach now commonly used to identify interactions between complex diseases [14,15,18,19,25,26]. Our analysis of these gene expressions patterns seen in AD and IS patients revealed numerous significant alterations, with expression profiles of 26 transcripts (22 unique genes) (termed “common DEGs”) that were found to be dysregulated in both transcriptomic datasets.…”

Section: Discussionmentioning

confidence: 99%

“…Clearly, both involve neurological damage, and it is possible that there are shared pathological mechanisms underlying both conditions [8,9,10]. Several studies have tried to identify genetic links between IS and AD, for example, by genome-wide association studies; these have identified common genetic elements, mainly single nucleotide polymorphisms in IS and AD that point to at least some shared element in their pathogenesis [10,11,12,13,14,15,16,17,18], but the significance of these is currently uncertain. Molecular components that are commonly dysregulated in both diseases is, to date, very limited in AD and IS.…”

Section: Introductionmentioning

confidence: 99%

“…Molecular components that are commonly dysregulated in both diseases is, to date, very limited in AD and IS. However, candidate biomarkers, such as differentially expressed genes (DEGs), have been identified using transcriptomic datasets from RNA-seq and microarray studies [14,15,18]. Therefore, to capitalize on the availability of these datasets, we have employed a systems biology approach to identify dysregulated genes and molecular pathways that are common to AD and IS affected tissues.…”

Section: Introductionmentioning

confidence: 99%

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Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets

Rahman¹,

Islam

Shahjaman

et al. 2019

Medicina

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Background and objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in severe dementia. Having ischemic strokes (IS) is one of the risk factors of the AD, but the molecular mechanisms that underlie IS and AD are not well understood. We thus aimed to identify common molecular biomarkers and pathways in IS and AD that can help predict the progression of these diseases and provide clues to important pathological mechanisms. Materials and Methods: We have analyzed the microarray gene expression datasets of IS and AD. To obtain robust results, combinatorial statistical methods were used to analyze the datasets and 26 transcripts (22 unique genes) were identified that were abnormally expressed in both IS and AD. Results: Gene Ontology (GO) and KEGG pathway analyses indicated that these 26 common dysregulated genes identified several altered molecular pathways: Alcoholism, MAPK signaling, glycine metabolism, serine metabolism, and threonine metabolism. Further protein–protein interactions (PPI) analysis revealed pathway hub proteins PDE9A, GNAO1, DUSP16, NTRK2, PGAM2, MAG, and TXLNA. Transcriptional and post-transcriptional components were then identified, and significant transcription factors (SPIB, SMAD3, and SOX2) found. Conclusions: Protein–drug interaction analysis revealed PDE9A has interaction with drugs caffeine, γ-glutamyl glycine, and 3-isobutyl-1-methyl-7H-xanthine. Thus, we identified novel putative links between pathological processes in IS and AD at transcripts levels, and identified possible mechanistic and gene expression links between IS and AD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets

Rahman¹,

Islam

Shahjaman

et al. 2019

Medicina

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“…Gene expression analysis using microarrays is a global and popular method to develop and refine the molecular determinants of human disorders that have proven to be a sensitive method. We used these technologies to analyze the gene expression profiles of Parkinson's disease (PD), Alzheimer's disease (AD), Lou Gehrig's disease (LGD), Epilepsy disease (ED) and Multiple Sclerosis disease (MSD) to find the effects of welding fumes on them [24,25]. To uniform the mRNA expression data of different platforms and to avoid the problems of experimental systems, we normalized the gene expression data (disease state or control data) by using the Z-score transformation (Z ij ) for each NDGD gene expression profile using…”

Section: Analysis Methodsmentioning

confidence: 99%

Genetic effects of welding fumes on the progression of neurodegenerative diseases

et al. 2019

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Background: Welding involves exposure to fumes, gases and radiant energy that can be hazardous to human health. Welding fumes (WFs) comprise a complex mixture of metallic oxides, silicates and fluorides that may result in different health effects. Inhalation of WFs in large quantities over a long periods may pose a risk of developing neurodegenerative diseases (NDGDs), but the nature of this risk is poorly understood. To address this we performed transcriptomic analysis to identify links between WF exposure and NDGDs. Methods: We developed quantitative frameworks to identify the gene expression relationships of WF exposure and NDGDs. We analyzed gene expression microarray data from fume-exposed tissues and NDGDs including Parkinson's disease (PD), Alzheimer's disease (AD), Lou Gehrig's disease (LGD), Epilepsy disease (ED) and multiple sclerosis disease (MSD) datasets. We constructed disease-gene relationship networks and identified dysregulated pathways, ontological pathways and protein-protein interaction sub-network using multilayer network topology and neighborhood-based benchmarking. Results: We observed that WF associated genes share 18, 16, 13, 19 and 19 differentially expressed genes with PD, AD, LGD, ED and MSD respectively. Gene expression dysregulation along with relationship networks, pathways and ontologic analysis indicate that WFs may be linked to the progression of these NDGDs. Conclusions: Our developed network-based approach to analysis and investigate the genetic effects of welding fumes on PD, AD, LGD, ED and MSD neurodegenerative diseases could be helpful to understand the causal influences of WF exposure for the progression of the NDGDs.

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“…Association studies also revealed links between the INPP5K gene and autophagy (Zirin et al, 2015), Parkinson (Nazeri et al, 2015;Zhu et al, 2018;Liu et al, 2019) and Alzheimer diseases (Rahman et al, 2020).…”

Section: Inpp5k Association With Other Biological Processes and Humanmentioning

confidence: 97%

The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions

Schurmans

Catsyne

Desmet

et al. 2021

Advances in Biological Regulation

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INPP5K (Inositol Polyphosphate 5-Phosphatase K, or SKIP (for Skeletal muscle and Kidney enriched Inositol Phosphatase) is a member of the phosphoinositide 5-phosphatases family. Its protein structure is comprised of a N-terminal catalytic domain which hydrolyses both PtdIns(4,5)P2 and PtdIns(3,4,5)P3, followed by a SKICH domain at the C-terminus which is responsible for protein-protein interactions and subcellular localization of INPP5K. Strikingly, INPP5K is mostly concentrated in the endoplasmic reticulum, although it is also detected at the plasma membrane, in the cytosol and the nucleus. Recently, mutations in INPP5K have been detected in patients with a rare form of autosomal recessive congenital muscular dystrophy with cataract, short stature and intellectual disability. INPP5K functions extend from control of insulin signaling, endoplasmic reticulum stress response and structural integrity, myoblast differentiation, cytoskeleton organization, cell adhesion and migration, renal osmoregulation, to cancer. The goal of this review is thus to summarize and comment recent and less recent data in the literature on INPP5K, in particular on the structure, expression, intracellular localization, interactions and functions of this specific member of the 5-phosphatases family.

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Identification of biomarkers and pathways to identify novel therapeutic targets in Alzheimer’s disease: Insights from a systems biomedicine perspective

Cited by 8 publications

References 80 publications

Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets

Discovering Biomarkers and Pathways Shared by Alzheimer’s Disease and Ischemic Stroke to Identify Novel Therapeutic Targets

Genetic effects of welding fumes on the progression of neurodegenerative diseases

The phosphoinositide 5-phosphatase INPP5K: From gene structure to in vivo functions

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