Oncogenic Pathways in Neurodegenerative Diseases

Varela, Luis; García-Rendueles, María E.R.

doi:10.3390/ijms23063223

Cited by 17 publications

(11 citation statements)

References 245 publications

(297 reference statements)

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“…For instance, it is well established that "oxidative phosphorylation" is involved in PD onset and progression and that the dysregulation of the same molecular signaling pathways, such as "MAPK signaling," are implicated in the onset and the progression of cancers and neurodegenerative diseases, including PD, Alzheimer's disease, and Huntington's disease, albeit with different outcomes. 15 Moreover, pathways related to the "regulation of the actin cytoskeleton" and "focal adhesion" were also dysregulated in this study. It has been shown that these can be altered in neurodegenerative disorders.…”

Section: Discussionmentioning

confidence: 55%

“…For instance, it is well established that “oxidative phosphorylation” is involved in PD onset and progression and that the dysregulation of the same molecular signaling pathways, such as “MAPK signaling,” are implicated in the onset and the progression of cancers and neurodegenerative diseases, including PD, Alzheimer’s disease, and Huntington’s disease, albeit with different outcomes. 15…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal dysregulation of long non-coding RNAs in Parkinson’s disease

Müller-Nedebock,

Cuttler,

Pfaff

et al. 2023

Exp Biol Med (Maywood)

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Long non-coding RNAs (lncRNAs) have been suggested as potential biomarkers for Parkinson’s disease (PD). This study aimed to identify blood-based lncRNA transcripts that are dysregulated in PD over time and could serve as peripheral biomarkers. Using RNA-sequencing data from the Parkinson’s Progression Markers Initiative, differential expression between case and control groups at five different time points was detected, and pathway analysis was conducted. Seven transcripts, not previously linked to PD, were consistently dysregulated across all time points, while PD-linked lncRNAs were dysregulated at some but not all time points. Pathway analysis highlighted pathways, known to be affected in PD. This suggested that dysregulated lncRNA transcripts could play a role in PD pathogenesis by affecting well-known PD pathways and highlighted their potential as longitudinal biomarkers for PD. Further studies are needed to validate these findings and explore the potential use of identified lncRNAs as diagnostic and therapeutic targets.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Longitudinal dysregulation of long non-coding RNAs in Parkinson’s disease

Müller-Nedebock,

Cuttler,

Pfaff

et al. 2023

Exp Biol Med (Maywood)

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“…The involvement of conventional oncogenic pathways are increasingly investigated in neurodegenerative disease, including AD. 53 In addition to MAPK and Ras, “PI3K-Akt signaling pathway” and “mTOR signaling pathway”, along with DEGs Cdk , Tgfb , Trp53 , and Wnt , were in our dataset and are implicated in cancer and, more recently, in AD. 53 Neuronal and synapse pathways were also represented in late-stage Pv- positive interneurons along with insulin resistance and several additional hormone pathways.…”

Section: Discussionmentioning

confidence: 91%

“…Similarly, MAPK signaling is a network that amplifies molecules promoting cell proliferation, growth, and survival. 53 Several MAPK signaling member levels are altered in AD, e.g ., p38, 54 JNK, 55 and their blockade alters amyloid burden. Mapk8 (JNK) was a DEG in our early-stage Vglut-positive dataset.…”

Section: Discussionmentioning

confidence: 99%

Regional interneuron transcriptional changes reveal pathologic markers of disease progression in a mouse model of Alzheimer’s disease

Chen,

Noureldein,

Rigan

et al. 2023

Preprint

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder and leading cause of dementia, characterized by neuronal and synapse loss, amyloid-β and tau protein aggregates, and a multifactorial pathology involving neuroinflammation, vascular dysfunction, and disrupted metabolism. Additionally, there is growing evidence of imbalance between neuronal excitation and inhibition in the AD brain secondary to dysfunction of parvalbumin (PV)- and somatostatin (SST)-positive interneurons, which differentially modulate neuronal activity. Importantly, impaired interneuron activity in AD may occur upstream of amyloid-β pathology rendering it a potential therapeutic target. To determine the underlying pathologic processes involved in interneuron dysfunction, we spatially profiled the brain transcriptome of the 5XFAD AD mouse model versus controls, across four brain regions, dentate gyrus, hippocampal CA1 and CA3, and cortex, at early-stage (12 weeks-of-age) and late-stage (30 weeks-of-age) disease. Global comparison of differentially expressed genes (DEGs) followed by enrichment analysis of 5XFAD versus control highlighted various biological pathways related to RNA and protein processing, transport, and clearance in early-stage disease and neurodegeneration pathways at late-stage disease. Early-stage DEGs examination found shared,e.g., RNA and protein biology, and distinct,e.g., N-glycan biosynthesis, pathways enriched in PV-versus somatostatin SST-positive interneurons and in excitatory neurons, which expressed neurodegenerative and axon- and synapse-related pathways. At late-stage disease, PV-positive interneurons featured cancer and cancer signaling pathways along with neuronal and synapse pathways, whereas SST-positive interneurons showcased glycan biosynthesis and various infection pathways. Late-state excitatory neurons were primarily characterized by neurodegenerative pathways. These fine-grained transcriptomic profiles for PV- and SST-positive interneurons in a time- and spatial-dependent manner offer new insight into potential AD pathophysiology and therapeutic targets.

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“…In cancers the cell survival and proliferation is increased, whereas, in NDDs those alterations lead to cell death and apoptosis. The most altered signal pathways in cancer, e.g., Nrf2 pathway and Wnt/β-catenin pathway, are also implicated in NDDs, like AD and PD ( Varela and Garcia-Rendueles, 2022 ).…”

Section: Kinase Inhibitors Used In Ndd Pathway Interrogationmentioning

confidence: 99%

CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders

Baier

Szyszka

2022

Front. Mol. Biosci.

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Casein kinases are involved in a variety of signaling pathways, and also in inflammation, cancer, and neurological diseases. Therefore, they are regarded as potential therapeutic targets for drug design. Recent studies have highlighted the importance of the casein kinase 1 superfamily as well as protein kinase CK2 in the development of several neurodegenerative pathologies, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. CK1 kinases and their closely related tau tubulin kinases as well as CK2 are found to be overexpressed in the mammalian brain. Numerous substrates have been detected which play crucial roles in neuronal and synaptic network functions and activities. The development of new substances for the treatment of these pathologies is in high demand. The impact of these kinases in the progress of neurodegenerative disorders, their bona fide substrates, and numerous natural and synthetic compounds which are able to inhibit CK1, TTBK, and CK2 are discussed in this review.

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Oncogenic Pathways in Neurodegenerative Diseases

Cited by 17 publications

References 245 publications

Longitudinal dysregulation of long non-coding RNAs in Parkinson’s disease

Longitudinal dysregulation of long non-coding RNAs in Parkinson’s disease

Regional interneuron transcriptional changes reveal pathologic markers of disease progression in a mouse model of Alzheimer’s disease

CK2 and protein kinases of the CK1 superfamily as targets for neurodegenerative disorders

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