Nogo‑66 promotes β‑amyloid protein secretion via NgR/ROCK‑dependent BACE1 activation

Xie, Qingqing; Feng, Xiao; Huang, Yi-Υun; Fang, Nian; Hua, Yuansheng; Wang, Zijian; Cao, Qiao-Υu; Lou, Guofeng; Jiang, Pan; Hu, Yang; Li, Fangcheng; Zheng, Qi; Xiao, Fei

doi:10.3892/mmr.2021.11827

Cited by 6 publications

(5 citation statements)

References 29 publications

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“…In addition, AD fractions were enriched with proteins such as kallikrein-4 (KLK4), flotilin-2 (FLOT2), RTN3 and RTN4 (the latter is also known as Nogo; Fig. 1C), which were previously shown to alter neuronal APP processing [68][69][70][71]. Furthermore, some proteins enriched in AD samples were shown to trigger Aβ fibrillation, such as syndecan-4 (SDC4) [72] and agrin [65], or, in contrast, increase the solubility of amyloid peptides such as SAP [73] and inhibit Aβ aggregation, such as HSPB1 [74] and MT3 [75].…”

Section: Discussionmentioning

confidence: 99%

Modeling the early stages of Alzheimer’s disease by administering intracerebroventricular injections of human native Aβ oligomers to rats

Baerends

Soud

Folke

et al. 2022

acta neuropathol commun

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Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease characterized by the accumulation of aggregated amyloid beta (Aβ) and hyperphosphorylated tau along with a slow decline in cognitive functions. Unlike advanced AD, the initial steps of AD pathophysiology have been poorly investigated, partially due to limited availability of animal models focused on the early, plaque-free stages of the disease. The aim of this study was to evaluate the early behavioral, anatomical and molecular alterations in wild-type rats following intracerebroventricular injections of human Aβ oligomers (AβOs). Bioactive human AD and nondemented control brain tissue extracts were characterized using ELISA and proteomics approaches. Following a bilateral infusion, rats underwent behavioral testing, including the elevated plus maze, social recognition test, Morris water maze and Y-maze within 6 weeks postinjection. An analysis of brain structure was performed with manganese-enhanced MRI. Collected brain tissues were analyzed using stereology, immunohistochemistry, ELISA and qPCR. No sensorimotor deficits affecting motor performance on different maze tasks were observed, nor was spatial memory disturbed in AD rats. In contrast, a significant impairment of social memory became evident at 21 days postinjection. This deficit was associated with a significantly decreased volume of the lateral entorhinal cortex and a tendency toward a decrease in the total brain volume. Significant increase of cleaved caspase-3-positive cells, microglial activation and proinflammatory responses accompanied by altered expression of synaptic markers were observed in the hippocampus of AD rats with immunohistochemical and qPCR approaches at 6 weeks postinjection. Our data suggest that the social memory impairment observed in AβO-injected rats might be determined by neuroinflammatory responses and synaptopathy. An infusion of native oligomeric Aβ in the rat brain represents a feasible tool to model early plaque-free events associated with AD.

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Section: Discussionmentioning

confidence: 99%

Modeling the early stages of Alzheimer’s disease by administering intracerebroventricular injections of human native Aβ oligomers to rats

Baerends

Soud

Folke

et al. 2022

acta neuropathol commun

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“…One of the potential biomarkers in ND seems to be RTN4 protein. The data from the available literature has suggested the relationship between RTNs and pathogenesis of neurodegenerative disease [16,20,37,38]. However, no studies on Alzheimer's and Parkinson's diseases have been reported in which the concentration of RTN4 in cerebrospinal fluid was assessed, and there are a few studies with respect to multiple sclerosis.…”

Section: Discussionmentioning

confidence: 99%

“…According to some authors, increased expression of RTN-4A is possibly related to accelerated β-amyloid production and deposition in senile plaques, which may lead to the onset and development of AD [17]. It seems that particularly Nogo-66, a major inhibitory region of RTN-4A, increases the production of Aβ40 and Aβ42 in a dose-dependent manner [20]. Interestingly, other members of RTN4 subfamily (RTN4B and RTN4C) and RTN3 decreased about 30-50% secretion of Aβ40 and Aβ42 [40].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have reported that RTN4A may promote amyloid β production in the brain by regulating the beta-site amyloid precursor proteincleaving enzyme1 (BACE1) function and APP processing [19]. The main part of the protein responsible for boosting of Aβ40 and Aβ42 production is Nogo-66 [20]. Nogo-66 binds to its receptor (NgR1) and regulates the generation of Aβ, activating BACE1 and increasing APP level via GTPases of the Rho family, RhoA kinase (ROCK), LimK, and cofilin [20].…”

Section: Introductionmentioning

confidence: 99%

“…The main part of the protein responsible for boosting of Aβ40 and Aβ42 production is Nogo-66 [20]. Nogo-66 binds to its receptor (NgR1) and regulates the generation of Aβ, activating BACE1 and increasing APP level via GTPases of the Rho family, RhoA kinase (ROCK), LimK, and cofilin [20]. Moreover, the activation of ROCK pathway accelerated Aβ42 production, while PKC activation decreases the Aβ 42 concentration [19,20].…”

Section: Introductionmentioning

confidence: 99%

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The Clinical Significance of Cerebrospinal Fluid Reticulon 4 (RTN4) Levels in the Differential Diagnosis of Neurodegenerative Diseases

Kulczyńska-Przybik

Dulewicz

Słowik

et al. 2021

JCM

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Neurodegenerative diseases (NDs) belong to the top global causes of mortality. Diagnostic approaches to improve early diagnosis and differentiation of these diseases are constantly being sought. Therefore, we aimed to assess the cerebrospinal fluid (CSF) concentrations of Reticulon 4 (RTN4) in patients with neurodegenerative diseases and evaluate the potential clinical usefulness of this protein. RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. According to our best knowledge, this is the first investigation providing the data concerning the dynamic of CSF RTN4 protein levels in patients with different NDs. Methods: Overall, 77 newly diagnosed patients with neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS), as well as 21 controls, were enrolled in the study. The CSF concentrations of tested proteins were assessed using immunological assays. Results: We revealed significantly higher CSF RTN4A levels in patients with AD, PD, and MS in comparison to the controls. Moreover, the comparative analysis of RTN4 concentration between different neurodegenerative diseases revealed the highest concentration of RTN4A in AD patients and a statistically significant difference between AD vs. PD, and AD vs. MS groups. The increased CSF level of the protein correlated with Tau, and pTau181 proteins in AD as well as in PD patients. Conclusions: Our study presents a previously not identified clinical utility of RTN4 in the differential diagnosis of neurodegenerative diseases.

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Unveiling the modulation of Nogo receptor in neuroregeneration and plasticity: Novel aspects and future horizon in a new frontier

Dave

Shah

et al. 2023

Biochemical Pharmacology

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Nogo‑66 promotes β‑amyloid protein secretion via NgR/ROCK‑dependent BACE1 activation

Cited by 6 publications

References 29 publications

Modeling the early stages of Alzheimer’s disease by administering intracerebroventricular injections of human native Aβ oligomers to rats

Modeling the early stages of Alzheimer’s disease by administering intracerebroventricular injections of human native Aβ oligomers to rats

The Clinical Significance of Cerebrospinal Fluid Reticulon 4 (RTN4) Levels in the Differential Diagnosis of Neurodegenerative Diseases

Unveiling the modulation of Nogo receptor in neuroregeneration and plasticity: Novel aspects and future horizon in a new frontier

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