Immunomodulation induced by central nervous system‐related peptides as a therapeutic strategy for neurodegenerative disorders

Palumbo, María Laura; Moroni, Alejandro David; Quiroga, Sofía; Castro, María Micaela; Burgueño, Adriana Laura; Genaro, Ana Marı́a

doi:10.1002/prp2.795

Cited by 9 publications

(4 citation statements)

References 95 publications

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“…In terms of immune cell infiltration, compared to non-ischemic stroke patients, ischemic stroke patients showed higher levels of γδ T cells, B cells, monocytes, M0 macrophages, activated dendritic cells, neutrophils, and activated mast cells; this finding was consistent with previous studies [19,20]. In ischemic stroke research, NLRP3 and its downstream proinflammatory cytokines have been extensively studied at an early stage [21,22].…”

Section: Discussionsupporting

confidence: 89%

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke

Liu,

Wu,

Tao

et al. 2023

NeuroReport

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The present study elucidated cuproptosis-related molecular clusters involved in ischemic stroke and developed predictive models. Transcriptomic and immunological profiles of ischemic stroke-related datasets were extracted from the Gene Expression Omnibus database. Next, we conducted weighted gene co-expression network analysis to determine cluster-specific differentially expressed genes (DEGs). Models such as random forest and eXtreme gradient boosting (XGB) were evaluated to select the best prediction performance model. Subsequently, we validated the model’s predictive efficiency by using nomograms, decision curve analysis, calibration curves, and receiver operating characteristic curve analysis with an external dataset. We identified two cuproptosis-related clusters involved in ischemic stroke. The DEGs in Cluster 2 were closely associated with amino acid metabolism, various immune responses, and cell proliferation pathways. The XGB model showed lower residuals, a smaller root mean square error, and a greater area under the curve value (AUC = 0.923), thus exhibiting the best discriminative performance. The AUC value for the external validation dataset was 0.921, thus confirming the high performance of the model. NFE2L2, NLRP3, GLS, LIPT1, and MTF1 were identified as potential cuproptosis predictors, thus shedding new light on ischemic stroke pathogenesis and heterogeneity.

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Section: Discussionsupporting

confidence: 89%

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke

Liu,

Wu,

Tao

et al. 2023

NeuroReport

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“…Protective autoimmunity of the body can also be exploited to modulate the immuno-microenvironment. A91, a peptide derived from the immunogenic sequence (87-99) of myelin-basic protein (MBP), exerts its anti-inflammatory effects by inhibiting lipid peroxidation, downregulating inducible nitric oxide synthase gene expression, reducing apoptosis, and inducing activation of Th2-lymphocytes that promote an M2 macrophage phenotype 135 . A91 immunization increased anti-inflammatory cytokines and neurotrophic factors and decreased proinflammatory cytokines, suggesting the potential for motor and sensory recovery improvement in the chronic stage of SCI.…”

Section: Promoting Neurogenesis Of Enspcs Located In the Sci Nichementioning

confidence: 99%

Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair

Li¹,

Luo²,

Xiao³

et al. 2023

Theranostics

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Traumatic spinal cord injury (SCI) can cause severe neurological impairments. Clinically available treatments are quite limited, with unsatisfactory remediation effects. Residing endogenous neural stem/progenitor cells (eNSPCs) tend to differentiate towards astrocytes, leaving only a small fraction towards oligodendrocytes and even fewer towards neurons; this has been suggested as one of the reasons for the failure of autonomous neuronal regeneration. Thus, finding ways to recruit and facilitate the differentiation of eNSPCs towards neurons has been considered a promising strategy for the noninvasive and immune-compatible treatment of SCI. The present manuscript first introduces the responses of eNSPCs after exogenous interventions to boost endogenous neurogenesis in various SCI models. Then, we focus on state-of-art manipulation approaches that enhance the intrinsic neurogenesis capacity and reconstruct the hostile microenvironment, mainly consisting of pharmacological treatments, stem cell-derived exosome administration, gene therapy, functional scaffold implantation, inflammation regulation, and inhibitory element delineation. Facing the extremely complex situation of SCI, combined treatments are also highlighted to provide more clues for future relevant investigations.

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“…Nevertheless, recent research studies have changed this belief by showing an active and constant interaction between the CNS and both the innate and adaptive peripheral immune systems. Novel reports affirm that in healthy individuals, the peripheral immune system and CNS constantly interact in order to maintain CNS integrity, adequate cognitive function and neurogenesis [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review

et al. 2023

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Neurodegenerative diseases (NDDs) are a major health problem worldwide. Statistics suggest that in America in 2030 there will be more than 12 million people suffering from a neurodegenerative pathology. Furthermore, the increase in life expectancy enhances the importance of finding new and better therapies for these pathologies. NDDs could be classified into chronic or acute, depending on the time required for the development of clinical symptoms and brain degeneration. Nevertheless, both chronic and acute stages share a common immune and inflammatory pathway in their pathophysiology. Immunization with neural-derived peptides (INDP) is a novel therapy that has been studied during the last decade. By inoculating neural-derived peptides obtained from the central nervous system (CNS), this therapy aims to boost protective autoimmunity, an autoreactive response that leads to a protective phenotype that produces a healing environment and neuroregeneration instead of causing damage. INDP has shown promising findings in studies performed either in vitro, in vivo or even in some pre-clinical trials of different NDDs, standing as a potentially beneficial therapy. In this review, we will describe some of the studies in which the effect of INDP strategies have been explored in different (chronic and acute) neurodegenerative diseases.

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Immunomodulation induced by central nervous system‐related peptides as a therapeutic strategy for neurodegenerative disorders

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 9 publications

References 95 publications

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke

Identification and immunological characterization of cuproptosis-related molecular clusters in ischemic stroke

Recent advances in endogenous neural stem/progenitor cell manipulation for spinal cord injury repair

Immunization with Neural-Derived Peptides in Neurodegenerative Diseases: A Narrative Review

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