Unraveling the genes implicated in Alzheimer's disease

Giri, Mohan; Shah, Abhilasha; Upreti, Bibhuti; Chamling, Jayanti

doi:10.3892/br.2017.927

Cited by 23 publications

(20 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this context, it is important to remark that VEGFA , IL-8 , and COL8A1 genes have also been indicated as key regulators of angiogenic mechanisms and have been associated with a higher susceptibility to AMD [1,5,13]. On the other hand, APBB2 has been extensively described in relation to its association with late-onset AD because of its role in processing amyloid precursor protein (APP) into β-amyloid [32]. Recent evidence hypothesized that APBB2 production may increase the formation and deposition of toxic β-amyloid both in neuronal and retinal cells [33,34].…”

Section: Discussionmentioning

confidence: 99%

The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A

Strafella

Errichiello

Caputo

et al. 2019

IJMS

View full text Add to dashboard Cite

The complex interplay among genetic, epigenetic, and environmental variables is the basis for the multifactorial origin of age-related macular degeneration (AMD). Previous results highlighted that single nucleotide polymorphisms (SNPs) of CFH, ARMS2, IL-8, TIMP3, SLC16A8, RAD51B, VEGFA, and COL8A1 were significantly associated with the risk of AMD in the Italian population. Given these data, this study aimed to investigate the impact of SNPs in genes coding for MIR146A, MIR31, MIR23A, MIR27A, MIR20A, and MIR150 on their susceptibility to AMD. Nine-hundred and seventy-six patients with exudative AMD and 1000 controls were subjected to an epigenotyping analysis through real-time PCR and direct sequencing. Biostatistical and bioinformatic analysis was performed to evaluate the association with susceptibility to AMD. These analyses reported that the SNPs rs11671784 (MIR27A, G/A) and rs2910164 (MIR146A, C/G) were significantly associated with AMD risk. Interestingly, the bioinformatic analysis showed that MIR27A and MIR146A take part in the angiogenic and inflammatory pathways underlying AMD etiopathogenesis. Thus, polymorphisms within the pre-miRNA sequences are likely to affect their functional activity, especially the interaction with specific targets. Therefore, our study represents a step forward in the comprehension of the mechanisms leading to AMD onset and progression, which certainly include the involvement of epigenetic modifications.

show abstract

Section: Discussionmentioning

confidence: 99%

The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A

Strafella

Errichiello

Caputo

et al. 2019

IJMS

View full text Add to dashboard Cite

show abstract

“…Alzheimer's disease (AD) is regarded as a chronic neurodegenerative disorder. It is considered to be the most common cause of dementia among aging people (Giri, Shah, Upreti, & Rai, 2017). AD is usually characterized by aggregations and depositions of many misfolded proteins and progressive cognitive dysfunction, which eventually lead to dementia and mortality (Bertram, Lill, & Tanzi, 2010).…”

Section: Introductionmentioning

confidence: 99%

Retracted: Effect of microRNA‐186 on oxidative stress injury of neuron by targeting interleukin 2 through the janus kinase‐signal transducer and activator of transcription pathway in a rat model of Alzheimer’s disease

Wen

Wang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Recent studies have proposed that microRNAs (miR) function as novel diagnostic and prognostic biomarkers and therapeutic targets in Alzheimer's disease (AD), a common disease among the elderly. In the current study, we aim to explore the effect of miR-186 on oxidative stress injury of neuron in rat models of AD with the involvement of the interleukin-2 (IL2) and the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. AD rat models were established, and dual-luciferase reporter assay and online software were used to confirm the targeting relationship between miR-186 and IL2. Immunohistochemistry was used evaluating the positive rate of IL2. Afterward, to define the role of miR-186 in AD, miR-186, IL2, and JAK-STAT related protein (JAK2, STAT3) expressions were quantified. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and cell apoptosis was detected by flow cytometry. We observed downregulated miR-186 and IL2 and upregulated JAK-STAT signaling pathway related genes in AD. The overexpression of miR-186 was shown to significantly promote cell proliferation while suppressing cell apoptosis along with the expression of the IL2 and JAK-STAT signaling pathway related protein. Collectively, the key findings obtained from the current study define the potential role of miR-186 as an inhibitor of AD development by downregulation of IL2 through suppression of the JAK-STAT signaling pathway.

show abstract

“…However, many of the canonical pathways noted in the present study, such as those involved in preapoptotic or apoptotic processes, were also prominent in the latter study 20 . The genes and pathways identified here in our acute Aβ neurotoxicity models are also in contrast to genes strongly correlated with late-onset AD, including apolipoprotein E (APOE), triggering receptor expressed on myeloid cells 2 (TREM2) and cluster of differentiation 33 (CD33) [21][22][23][24] among others, suggesting differences in gene regulation with early rises in Aβ in brain (prodromic period) as compared to AD.…”

Section: Discussionmentioning

confidence: 87%

Transcriptome Profile of Nicotinic Receptor-Linked Sensitization of Beta Amyloid Neurotoxicity

Arora

Belcaid

Lantz

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Understanding the specific gene changes underlying the prodromic stages of Alzheimer's disease pathogenesis will aid the development of new, targeted therapeutic strategies for this neurodegenerative disorder. Here, we employed RNA-sequencing to analyze global differential gene expression in a defined model nerve cell line expressing α4β2 nicotinic receptors (nAChRs), high-affinity targets for beta amyloid (Aβ). The nAChR-expressing neuronal cells were treated with nanomolar Aβ 1-42 to gain insights into the molecular mechanisms underlying Aβ-induced neurotoxicity in the presence of this sensitizing target receptor. We identified 15 genes (out of 15,336) that were differentially expressed upon receptor-linked Aβ treatment. Genes up-regulated with Aβ treatment were associated with calcium signaling and axonal vesicle transport (including the α4 nAChR subunit, the calcineurin regulator RCAN3, and KIF1C of the kinesin family). Downregulated genes were associated with metabolic, apoptotic or DNA repair pathways (including APBA3, PARP1 and RAB11). Validation of the differential expression was performed via qRT-PCR and immunoblot analysis in the defined model nerve cell line and primary mouse neurons. Further verification was performed using immunocytochemistry. In conclusion, we identified apparent changes in gene expression on Aβ treatment in the presence of the sensitizing nAChRs, linked to early-stage Aβ-induced neurotoxicity, which may represent novel therapeutic targets. Amyloid-β (Aβ) is a short, potentially neurotoxic peptide derived from amyloid precursor protein (APP) in select regions of the brain 1,2. At "physiological" levels (pM), there is considerable evidence for Aβ functioning as a positive neuromodulator 3-7 , acting through neuronal signaling receptors. In Alzheimer's disease (AD), a progressive neurodegenerative disorder that is the most prevalent cause of dementia, histopathology is mainly characterized by extracellular plaques composed primarily of the Aβ peptide in fibrillar form, intracellular neurofibrillary tangles formed from hyperphosphorylated tau, and neuronal degeneration including extensive loss of cholinergic basal forebrain neurons. In addition, synaptic impairment and loss are central to changes in memory and cognition in AD 8. Notably, during the prodromic phase of AD, soluble oligomeric Aβ levels are dramatically increased (high nM to μM) years before diagnosis (see 9). There is ample evidence that it is the diffusible oligomeric Aβ assemblies that play a role in neurotoxicity 10 and contribute to driving development of synaptic impairment and degeneration, largely through induction of abnormal tau and, later, neuroinflammation 11,12. There remain important questions, however, in regard to the impact of elevated Aβ levels on neuronal function, integrity and viability, in particular altered signaling through known target receptors. Despite extensive understanding of the pathology of AD, differential diagnosis of the disease in the prodromic and early stages has been problematic, part...

show abstract

Unraveling the genes implicated in Alzheimer's disease

Cited by 23 publications

References 125 publications

The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A

The Interplay between miRNA-Related Variants and Age-Related Macular Degeneration: EVIDENCE of Association of MIR146A and MIR27A

Retracted: Effect of microRNA‐186 on oxidative stress injury of neuron by targeting interleukin 2 through the janus kinase‐signal transducer and activator of transcription pathway in a rat model of Alzheimer’s disease

Transcriptome Profile of Nicotinic Receptor-Linked Sensitization of Beta Amyloid Neurotoxicity

Contact Info

Product

Resources

About