PICALM mRNA Expression in the Blood of Patients with Neurodegenerative Diseases and Geriatric Depression

Kumon, Hiroshi; Yoshino, Yuta; Funahashi, Yu; Mori, Hajime; Ueno, Mariko; Ozaki, Yuki; Yamazaki, Kiyohiro; Ochi, Shinichiro; Mori, Takaaki; Iga, Jun‐ichi; Nagai, Masahiro; Nomoto, Masahiro; Ueno, Shu‐ichi

doi:10.3233/jad-201046

Cited by 15 publications

(10 citation statements)

References 47 publications

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“…Berchtold NC et al used a microarray method to obtain RNA expression profiles in different postmortem brain regions of AD patients, including the postcentral gyrus, superior frontal gyrus, entorhinal cortex and hippocampus [ 6 ]. GSE48350 has also been used in some other studies [ 7–12 ]. In these studies, however, other factors (e.g., immunity, aging, toxicity) and samples (e.g., cortex, blood) are analyzed.…”

Section: Introductionmentioning

confidence: 99%

Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease

Liu

Jiang

et al. 2021

Bioengineered

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Alzheimer’s Disease (AD) is a neurodegenerative disease featured by cognitive impairment. This bioinformatic analysis was used to identify hub genes related to cognitive dysfunction in AD. The gene expression profile GSE48350 in the hippocampus of AD patients aged >70 years was obtained from the Gene Expression Omnibus (GEO) database. A total of 96 differentially expressed genes (DEGs) were identified, and subjected to Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses; a protein–protein interaction (PPI) network was constructed. The DEGs were enriched in synapse-related changes. A protein cluster was teased out of PPI. Furthermore, the cognition ranked the first among all the terms of biological process (BP). Next, 4 of 10 hub genes enriched in cognition were identified. The function of these genes was validated using APP/PS1 mice. Cognitive performance was validated by Morris Water Maze (MWM), and gene expression by RT-qPCR, Cholecystokinin ( CCK ), Tachykinin precursor 1 ( TAC1 ), Calbindin 1 ( CALB1 ) were downregulated in the hippocampus. These genes can provide new directions in the research of the molecular mechanism of AD.

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Section: Introductionmentioning

confidence: 99%

Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease

Liu

Jiang

et al. 2021

Bioengineered

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“…It was noted that phosphorylation of PKCδ, PICALM, and CDC37 were specifically enhanced in the tumor group, but few were identified in NT group. Among these three proteins, only PKCδ is directly involved in immune responses [21], while PICALM is a clathrin assemble protein [22], and CDC37 is a chaperone directing Hsp90 to its target kinases [23]. Given these, we hypothesized that PKCδ serves as the critical mediator for inducing immunosuppressive TME in EGFR-mutated lung cancer.…”

Section: Resultsmentioning

confidence: 99%

Tumor PKCδ instigates immune exclusion in EGFR-mutated non–small cell lung cancer

Zuo

Gao

Xie

et al. 2022

BMC Med

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Background The recruitment of a sufficient number of immune cells to induce an inflamed tumor microenvironment (TME) is a prerequisite for effective response to cancer immunotherapy. The immunological phenotypes in the TME of EGFR–mutated lung cancer were characterized as non-inflamed, for which immunotherapy is largely ineffective. Methods Global proteomic and phosphoproteomic data from lung cancer tissues were analyzed aiming to map proteins related to non-inflamed TME. The ex vivo and in vivo studies were carried out to evaluate the anti-tumor effect. Proteomics was applied to identify the potential target and signaling pathways. CRISPR-Cas9 was used to knock out target genes. The changes of immune cells were monitored by flow cytometry. The correlation between PKCδ and PD-L1 was verified by clinical samples. Results We proposed that PKCδ, a gatekeeper of immune homeostasis with kinase activity, is responsible for the un-inflamed phenotype in EGFR-mutated lung tumors. It promotes tumor progression by stimulating extracellular matrix (ECM) and PD-L1 expression which leads to immune exclusion and assists cancer cell escape from T cell surveillance. Ablation of PKCδ enhances the intratumoral penetration of T cells and suppresses the growth of tumors. Furthermore, blocking PKCδ significantly sensitizes the tumor to immune checkpoint blockade (ICB) therapy (αPD-1) in vitro and in vivo model. Conclusions These findings revealed that PKCδ is a critical switch to induce inflamed tumors and consequently enhances the efficacy of ICB therapy in EGFR-mutated lung cancer. This opens a new avenue for applying immunotherapy against recalcitrant tumors. Graphical Abstract

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“…To the best of our knowledge, this is the first study to show that specific clinical symptoms such as “insomnia early,” “insight,” and “recall” were associated with a diagnosis of dementia in late-life depression. To date, no easy and useful examinations have been available in clinical practice for a differential diagnosis between late-life depression with and without dementia based on specific depressive symptoms, although many previous studies have attempted to identify effective biological markers [ 30–34 ]. The results of the present study indicate that “insomnia early” and “insight” on the HAMD-17 and “recall” on the MMSE may be useful for differentiating late-life MDD with from that without dementia.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Comorbid Dementia in Late-life Depression and Bipolar Disorder: A Retrospective Inpatient Study

Ochi

Mori

Iga

et al. 2022

ADR

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Background: Dementia in patients with late-life mood disorders is clinically important. Objective: We aimed to investigate the prevalence of dementia in patients with late-life major depressive disorder (MDD) or bipolar disorder (BD) and to clarify the clinical characteristics associated with the diagnosis of dementia. Methods: The prevalence of dementia at hospital discharge and the clinical characteristics at hospitalization who are diagnosed with MDD or BD over 65 years of age, from the medical records of 684 patients who had been admitted from 2015 to 2020 were investigated. Results: A total of 66 patients with MDD (n = 50) and BD (n = 16) were analyzed. The prevalence of dementia was significantly higher in MDD than in BD (24.0% versus 0% ; p = 0.026). The mean age at onset of MDD was significantly older in the MDD with dementia group than in the MDD without (76.9±6.3 years versus 62.2±14.0 years; p < 0.001). The rate of first depressive episode at this admission was significantly higher in the MDD with dementia group (91.7% versus 30.3% ; p < 0.001). The diagnosis of dementia was significantly associated with lower scores for “insomnia early” (p = 0.019) and higher scores for “insight” (p = 0.049) on the 17-item Hamilton Depression Rating (HAMD-17) subscales and lower scores for “recall” (p = 0.003) on the MMSE subscales. Conclusion: The older age of first onset of depression, “insomnia early”, “insight” and “recall” may be useful indicators for a diagnosis of dementia in late-life depression.

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PICALM mRNA Expression in the Blood of Patients with Neurodegenerative Diseases and Geriatric Depression

Cited by 15 publications

References 47 publications

Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease

Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease

Tumor PKCδ instigates immune exclusion in EGFR-mutated non–small cell lung cancer

Prevalence of Comorbid Dementia in Late-life Depression and Bipolar Disorder: A Retrospective Inpatient Study

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