Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease

Jeon, Min‐Tae; Kim, Kyu-Sung; Kim, Eun Sun; Lee, Suji; Kim, Jieun; Hoe, Hyang‐Sook; Kim, Do-Geun

doi:10.1016/j.arr.2021.101333

Cited by 46 publications

(36 citation statements)

References 198 publications

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“…By contrast, Cln3 -deficient astrocytes more readily secreted fibrinogen and the mitogen C-reactive protein (CPR). Since fibrinogen and CPR are also neuroprotective ( Jeon et al, 2021 ), their increased extracellular presence could reflect an attempt by Cln3 -deficient astrocytes to counteract the neurodegenerative process. Together, these data indicate that cell–cell communication through secreted factors is perturbed in brain from a CLN3 diesease mouse model, which is consistent with observations of altered signaling in D. discoideum cln3 − cells ( Huber et al, 2014 , 2017 ; Huber, 2017 ).…”

Section: Potential Biomarkers Identified In Animal Models and Humansmentioning

confidence: 99%

Altered protein secretion in Batten disease

Huber

2021

Disease Models &Amp; Mechanisms

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The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are a group of neurological diseases that affect all ages and ethnicities worldwide. There are 13 different subtypes of NCL, each caused by a mutation in a distinct gene. The NCLs are characterized by the accumulation of undigestible lipids and proteins in various cell types. This leads to progressive neurodegeneration and clinical symptoms including vision loss, progressive motor and cognitive decline, seizures, and premature death. These diseases have commonly been characterized by lysosomal defects leading to the accumulation of undigestible material but further research on the NCLs suggests that altered protein secretion may also play an important role. This has been strengthened by recent work in biomedical model organisms, including Dictyostelium discoideum, mice, and sheep. Research in D. discoideum has reported the extracellular localization of some NCL-related proteins and the effects of NCL-related gene loss on protein secretion during unicellular growth and multicellular development. Aberrant protein secretion has also been observed in mammalian models of NCL, which has allowed examination of patient-derived cerebrospinal fluid and urine for potential diagnostic and prognostic biomarkers. Accumulated evidence links seven of the 13 known NCL-related genes to protein secretion, suggesting that altered secretion is a common hallmark of multiple NCL subtypes. This Review highlights the impact of altered protein secretion in the NCLs, identifies potential biomarkers of interest and suggests that future work in this area can provide new therapeutic insight.

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Section: Potential Biomarkers Identified In Animal Models and Humansmentioning

confidence: 99%

Altered protein secretion in Batten disease

Huber

2021

Disease Models &Amp; Mechanisms

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“…It is easily measured through a blood sample also in its high-sensitivity form (hs-CRP) [31] and used in clinical practice mainly as a biomarker of infection, chronic disease state, and chronic low-grade inflammation [30,32]. CRP usually does not freely cross BBB [33], even though several mechanisms have been hypothesized to explain how CRP can interact with the Central Nervous System (CNS) [33,34]. For instance, it has been suggested that an increase of the blood-brain barrier (BBB) permeability could be determined by severe stress and/or traumatic brain injury [35,36].…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein as a Biomarker for Major Depressive Disorder?

Orsolini

Pompili

Valenta

et al. 2022

IJMS

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The etiopathogenesis of depression is not entirely understood. Several studies have investigated the role of inflammation in major depressive disorder. The present work aims to review the literature on the association between C-Reactive Protein (CRP) and depression. A systematic review was performed for the topics of ‘CRP’ and ‘depression’ using the PubMed database from inception to December 2021. Fifty-six studies were identified and included in the review. Evidence suggested the presence of dysregulation in the inflammation system in individuals with depression. In most studies, higher blood CRP levels were associated with greater symptom severity, a specific pattern of depressive symptoms, and a worse response to treatment. Moreover, about one-third of depressed patients showed a low-grade inflammatory state, suggesting the presence of a different major depressive disorder (MDD) subgroup with a distinct etiopathogenesis, clinical course, treatment response, and prognosis, which could benefit from monitoring of CRP levels and might potentially respond to anti-inflammatory treatments. This work provides robust evidence about the potential role of CRP and its blood levels in depressive disorders. These findings can be relevant to developing new therapeutic strategies and better understanding if CRP may be considered a valuable biomarker for depression.

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“…The BBB maintains the independent circulation of CSF and microenvironment homeostasis for the brain tissue ( Sweeney et al, 2019 ). However, the BBB also brings significant challenges to diagnosis and treat brain tumors ( Jeon et al, 2021 ; Pottoo et al, 2021 ). For instance, most tumor-specific antigens are confined within this barrier, and their systematic detection can be problematic.…”

Section: Functions and Characteristics Of Cerebrospinal Fluidmentioning

confidence: 99%

“…The 5- and 10-year survival rates for central nervous system (CNS) tumors are about 36% and 31%, respectively. For the patients with newly diagnosed glioblastoma, the most malignant form of brain tumor, the median survival duration does not exceed 2 years ( Martinez-Rios et al, 2016 ; Duffau, 2017 ; Jeon et al, 2021 ; Rankin-Turner et al, 2021 ; Reddy et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Evolving Landscape of Long Non-coding RNAs in Cerebrospinal Fluid: A Key Role From Diagnosis to Therapy in Brain Tumors

Jiang

Gabriel

et al. 2021

Front. Cell Dev. Biol.

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Long non-coding RNAs (lncRNAs) are a type of non-coding RNAs that act as molecular fingerprints and modulators of many pathophysiological processes, particularly in cancer. Specifically, lncRNAs can be involved in the pathogenesis and progression of brain tumors, affecting stemness/differentiation, replication, invasion, survival, DNA damage response, and chromatin dynamics. Furthermore, the aberrations in the expressions of these transcripts can promote treatment resistance, leading to tumor recurrence. The development of next-generation sequencing technologies and the creation of lncRNA-specific microarrays have boosted the study of lncRNA etiology. Cerebrospinal fluid (CSF) directly mirrors the biological fluid of biochemical processes in the brain. It can be enriched for small molecules, peptides, or proteins released by the neurons of the central nervous system (CNS) or immune cells. Therefore, strategies that identify and target CSF lncRNAs may be attractive as early diagnostic and therapeutic options. In this review, we have reviewed the studies on CSF lncRNAs in the context of brain tumor pathogenesis and progression and discuss their potential as biomarkers and therapeutic targets.

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Emerging pathogenic role of peripheral blood factors following BBB disruption in neurodegenerative disease

Cited by 46 publications

References 198 publications

Altered protein secretion in Batten disease

Altered protein secretion in Batten disease

C-Reactive Protein as a Biomarker for Major Depressive Disorder?

Evolving Landscape of Long Non-coding RNAs in Cerebrospinal Fluid: A Key Role From Diagnosis to Therapy in Brain Tumors

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