Intranasal interferon beta improves memory and modulates inflammatory responses in a mutant APP-overexpressing rat model of Alzheimer’s disease

Chavoshinezhad, Sara; Kouchesfahani, Homa Mohseni; Salehi, Mohammad Saied; Pandamooz, Sareh; Ahmadiani, Abolhassan; Dargahi, Leila

doi:10.1016/j.brainresbull.2019.06.015

Cited by 16 publications

(3 citation statements)

References 91 publications

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“…In parallel, previous studies showed that rhEPO attenuates Parkinson’s disease-induced motor deficits (Thompson et al 2020 ) and protects against cognitive impairment (Sayed et al 2019 ) in mice. Likewise, IFN-β is reported to ameliorate cognitive dysfunction in rat models of Alzheimer’s disease (Chavoshinezhad et al 2019a , b ).…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin and interferon-β-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK/STAT signaling pathway

2022

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Abstract3-Nitropropionic acid (3-NP) model serves as a beneficial tool to evaluate the effect of novel treatments for Huntington’s disease (HD). The aim of the present study was to demonstrate the neuroprotective effect of recombinant human erythropoietin (rhEPO) and interferon-beta-1b (IFN-β-1b) in 3-NP-induced neurotoxicity in rats. Rats were injected with 3-NP (10 mg/kg/day, i.p) for 2 weeks and were divided into five subgroups; the first served as the HD group, the second received rhEPO (5000 IU/kg/every other day, i.p.) for 2 weeks, the third received rhEPO starting from the 5th day of 3-NP injection, the fourth received IFN-β-1b (300,000 units, every day other day, s.c) for 2 weeks, and the last received IFN-β-1b starting from the 5th day of 3-NP injection. All treatments significantly improved motor and behavior performance of rats. Moreover, all treatments markedly restored mitochondrial function as well as brain-derived neurotrophic factor level, and reduced oxidative stress biomarkers, pro-inflammatory mediators, nuclear factor kappa B expression, caspase-3, and Bax/Bcl2 ratio in the striatum. In conclusion, the present study demonstrates the neuroprotective potential of rhEPO or IFN-β-1b on 3-NP-induced neurotoxicity in rats. Furthermore, our study suggests that activation of JAK2/STAT3 or JAK1/STAT3 may contribute to the neuroprotective activity of rhEPO or IFN-β-1b, respectively. We also found that early treatment with rhEPO did not confer any benefits compared with late rhEPO treatment, while early IFN-β-1b showed a marked significant benefit compared with late IFN-β-1b.

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Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin and interferon-β-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK/STAT signaling pathway

2022

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“…APP overexpression by lentiviral transduction or Aβ 1−42 peptide delivery to the mouse brain induces pro-inflammatory cytokine production. This can be reduced by administration of IFN-β, consistent with the anti-inflammatory effects of type-I IFN (Chavoshinezhad et al, 2019;Mudò et al, 2019). Furthermore, genetic knockout of IFN-β is associated with reduced autophagic clearance and accumulation of ubiquitinated alpha-synuclein aggregates in mice (Ejlerskov et al, 2015).…”

Section: The Role Of Type-i Ifns In Disease Pathologymentioning

confidence: 55%

Type-I Interferons in Alzheimer's Disease and Other Tauopathies

Sanford

McEwan

2022

Front. Cell. Neurosci.

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The detection of pathogen-associated molecular patterns can elicit the production of type-I interferons (IFNs), soluble cytokines that induce a transcriptional state inhibitory to viral replication. Signatures of type-I IFN-driven gene expression, and type-I IFNs themselves, are observed in the central nervous system during neurodegenerative diseases including Alzheimer's disease and other tauopathies, the umbrella term for diseases that feature aggregation of the cytosolic protein tau. The contribution of the type-I IFN response to pathological progression of these diseases, however, is not well-understood. The wholesale transcriptional changes that ensue from type-I IFN production can both promote protective effects and lead to damage dependent on the context and duration of the response. The type-I IFN system therefore represents a signaling pathway with a potential disease-modifying role in the progression of neurodegenerative disease. In this review we summarize the evidence for a type-I IFN signature in AD and other tauopathies and examine the role of aggregated proteins as inflammatory stimuli. We explore both the protective role of IFN against protein pathologies as well as their downstream toxic consequences, which include the exacerbation of protein pathology as a potentially destructive feed-forward loop. Given the involvement of type-I IFNs in other neurogenerative diseases, we draw comparisons with other categories of homotypic protein aggregation. Understanding how type-I IFN influences progression of AD and other tauopathies may yield important insight to neurodegeneration and identify new targets in an area currently lacking disease-modifying therapies.

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“…It follows that the results obtained in humans may differ from the expected ones, based on preclinical evidence in rodents [9,102]. However, the N2B route has also been proven to be effective in delivering interferon-β (IFN-β) in rats [103,104] as well as in adult cynomolgus monkeys [78], whose nasal compartment exhibits a similar morphology to that of humans. In particular, the study conducted by Thorne et al, in accordance with previously obtained results in rats, underlined the ability of [ 125 I]-IFN-β1b to enter the primate CNS along the olfactory and trigeminal routes [78].…”

Section: Delivering Biotherapeutics Through the Intranasal Route Of A...mentioning

confidence: 99%

Cell-Penetrating Peptides as Valuable Tools for Nose-to-Brain Delivery of Biological Drugs

De Martini,

Sulmona,

Brambilla

et al. 2023

Cells

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Due to their high specificity toward the target and their low toxicity, biological drugs have been successfully employed in a wide range of therapeutic areas. It is yet to be mentioned that biologics exhibit unfavorable pharmacokinetic properties, are susceptible to degradation by endogenous enzymes, and cannot penetrate biological barriers such as the blood–brain barrier (i.e., the major impediment to reaching the central nervous system (CNS)). Attempts to overcome these issues have been made by exploiting the intracerebroventricular and intrathecal routes of administration. The invasiveness and impracticality of these procedures has, however, prompted the development of novel drug delivery strategies including the intranasal route of administration. This represents a non-invasive way to achieve the CNS, reducing systemic exposure. Nonetheless, biotherapeutics strive to penetrate the nasal epithelium, raising the possibility that direct delivery to the nervous system may not be straightforward. To maximize the advantages of the intranasal route, new approaches have been proposed including the use of cell-penetrating peptides (CPPs) and CPP-functionalized nanosystems. This review aims at describing the most impactful attempts in using CPPs as carriers for the nose-to-brain delivery of biologics by analyzing their positive and negative aspects.

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Intranasal interferon beta improves memory and modulates inflammatory responses in a mutant APP-overexpressing rat model of Alzheimer’s disease

Cited by 16 publications

References 91 publications

Recombinant human erythropoietin and interferon-β-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK/STAT signaling pathway

Recombinant human erythropoietin and interferon-β-1b protect against 3-nitropropionic acid-induced neurotoxicity in rats: possible role of JAK/STAT signaling pathway

Type-I Interferons in Alzheimer's Disease and Other Tauopathies

Cell-Penetrating Peptides as Valuable Tools for Nose-to-Brain Delivery of Biological Drugs

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