Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Beletskiy, Alexander; Чеснокова, Е. А.; Bal, Natalia

doi:10.3390/ijms22041849

Cited by 25 publications

(22 citation statements)

References 300 publications

(639 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Third, the spatial domains detected by SpatialPCA allowed us to identify region specific markers that are not identified by other methods. For example, only SpatialPCA detected the enrichment of Itpka, Igfbp4 and Map4 in the CA1 region of the hippocampus, consistent with their known enrichment pattern in the hippocampus pyramidal neurons [53][54][55] (Figure 4e). Other marker genes that are highly expressed in the substructures of the hippocampus are shown in Figure 4d.…”

Section: Mouse Hippocampus Data By Slide-seq V2supporting

confidence: 74%

Spatially Aware Dimension Reduction for Spatial Transcriptomics

Shang

Zhou

2022

Preprint

View full text Add to dashboard Cite

Spatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with enriched biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored and novel analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for spatial domain detection and explores its utility for trajectory inference on the tissue and for high-resolution spatial map construction. In the real data applications, SpatialPCA identifies key molecular and immunological signatures in a newly detected tumor surrounding microenvironment, including a tertiary lymphoid structure that shapes the gradual transcriptomic transition during tumorigenesis and metastasis. In addition, SpatialPCA detects the past neuronal developmental history that underlies the current transcriptomic landscape across tissue locations in the cortex.

show abstract

Section: Mouse Hippocampus Data By Slide-seq V2supporting

confidence: 74%

Spatially Aware Dimension Reduction for Spatial Transcriptomics

Shang

Zhou

2022

Preprint

View full text Add to dashboard Cite

show abstract

“…sAPPα (and BDNF) share some common functionalities with Insulin-like Growth Factor 2 (IGF2), and memory retention and LTP can be enhanced and ‘forgetting’ prevented by the addition of endogenous Insulin-like Growth Factor 2 (IGF2) [ 82 , 83 ]. A study analysing astrocyte protein secretion and gene expression in three mouse models of genetic neurodegenerative diseases (Rett, Fragile X and Down syndrome) showed that astrocytes secrete the IGF2 inhibitory protein IGFBP2, causing learning and memory failure [ 84 ].…”

Section: Discussionmentioning

confidence: 99%

Secreted Amyloid Precursor Protein Alpha (sAPPα) Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes

Peppercorn

Kleffmann

Hughes

et al. 2023

IJMS

View full text Add to dashboard Cite

Secreted amyloid precursor protein alpha (sAPPα), processed from a parent mammalian brain protein, amyloid precursor protein, can modulate learning and memory. Recently it has been shown to modulate the transcriptome and proteome of human neurons, including proteins with neurological functions. Here, we analysed whether the acute administration of sAPPα facilitated changes in the proteome and secretome of mouse primary astrocytes in culture. Astrocytes contribute to the neuronal processes of neurogenesis, synaptogenesis and synaptic plasticity. Cortical mouse astrocytes in culture were exposed to 1 nM sAPPα, and changes in both the whole-cell proteome (2 h) and the secretome (6 h) were identified with Sequential Window Acquisition of All Theoretical Fragment Ion Spectra–Mass Spectrometry (SWATH-MS). Differentially regulated proteins were identified in both the cellular proteome and secretome that are involved with neurologically related functions of the normal physiology of the brain and central nervous system. Groups of proteins have a relationship to APP and have roles in the modulation of cell morphology, vesicle dynamics and the myelin sheath. Some are related to pathways containing proteins whose genes have been previously implicated in Alzheimer’s disease (AD). The secretome is also enriched in proteins related to Insulin Growth Factor 2 (IGF2) signaling and the extracellular matrix (ECM). There is the promise that a more specific investigation of these proteins will help to understand the mechanisms of how sAPPα signaling affects memory formation.

show abstract

“…Igf2 was increased after treatment with anti-C1-INH, and combined RT and anti-C1-INH compared to control. Igf2 has been demonstrated in the brain of rodents, possibly increased in hippocampus and neural stem cells [ 35 ]. Thbs1 was increased in all treated groups compared to control.…”

Section: Resultsmentioning

confidence: 99%

Combined anti-C1-INH and radiotherapy against glioblastoma

et al. 2023

View full text Add to dashboard Cite

Background A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting. Methods Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately. Results In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals. Conclusions Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.

show abstract

Insulin-Like Growth Factor 2 As a Possible Neuroprotective Agent and Memory Enhancer—Its Comparative Expression, Processing and Signaling in Mammalian CNS

Cited by 25 publications

References 300 publications

Spatially Aware Dimension Reduction for Spatial Transcriptomics

Spatially Aware Dimension Reduction for Spatial Transcriptomics

Secreted Amyloid Precursor Protein Alpha (sAPPα) Regulates the Cellular Proteome and Secretome of Mouse Primary Astrocytes

Combined anti-C1-INH and radiotherapy against glioblastoma

Contact Info

Product

Resources

About