Interleukin-1 Promotes Expression and Phosphorylation of Neurofilament and tau Proteins in Vivo

doi:10.1006/exnr.2000.7393

Experimental Neurology

Volume 163, Issue 2, June 2000, Pages 388-391

https://doi.org/10.1006/exnr.2000.7393 Get rights and content

Abstract

Slow-release, IL-1-impregnated pellets implanted in rat cerebral cortex to simulate chronic overexpression of IL-1 significantly increased relative tissue levels of tau mRNA and of tau immunoreactivity in neuronal cell bodies and in swollen dystrophic neurites that also overexpressed phosphorylated and nonphosphorylated neurofilament epitopes. In addition, rats with IL-1-impregnated pellets, but not control rats or those with sham pellets, showed focal immunoreactivity for hyperphosphorylated tau epitopes present in paired helical filaments. Our results are consistent with an important driving role for IL-1 in the pathogenesis of Alzheimer-type neuronal and neuritic changes.

References (19)

C.B. Chambers et al.
Tau mRNA isoforms following sciatic nerve axotomy with and without regeneration
Mol. Brain Res.
(1997)
W.S.T. Griffin et al.
Senescence-accelerated overexpression of S100β in brain of SAMP6 mice
Neurobiol. Aging
(1998)
G.R. Guy et al.
Inactivation of a redox-sensitive protein phosphatase during the early events of tumor necrosis factor/interleukin-1 signal transduction
J. Biol. Chem.
(1993)
M. Morishima-Kawashima et al.
Hyperphosphorylation of tau in PHF
Neurobiol. Aging
(1995)
R.E. Mrak et al.
Glial cytokines in Alzheimer's disease. Review and pathogenic implications
Hum. Pathol.
(1995)
L.A.J O'Neill
Towards an understanding of the signal transduction pathways for interleukin 1
Biochim. Biophys. Acta
(1995)
N.J Rothwell
Functions and mechanisms of interleukin 1 in the brain
Trends Pharmacol. Sci.
(1991)
J.G. Sheng et al.
In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis
Neurobiol. Aging
(1996)
J.H. Su et al.
Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments
Brain Res.
(1996)

There are more references available in the full text version of this article.

Cited by (130)

Alzheimer's-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets
2024, iScience
Alzheimer’s disease (AD) is characterized by peri-neuronal amyloid plaque and intra-neuronal neurofibrillary tangles. These aggregates are identified by the immunodetection of “seed” proteins (Aβ_1–42 and hyperphosphorylated tau, respectively), but include many other proteins incorporated nonrandomly. Using click-chemistry intra-aggregate crosslinking, we previously modeled amyloid “contactomes” in SY5Y-APP_Sw neuroblastoma cells, revealing that aspirin impedes aggregate growth and complexity. By an analogous strategy, we now construct amyloid-specific aggregate interactomes of AD and age-matched-control hippocampi. Comparing these interactomes reveals AD-specific interactions, from which neural-network (NN) analyses predict proteins with the highest impact on pathogenic aggregate formation and/or stability. RNAi knockdowns of implicated proteins, in C. elegans and human-cell-culture models of AD, validated those predictions. Gene-Ontology meta-analysis of AD-enriched influential proteins highlighted the involvement of mitochondrial and cytoplasmic compartments in AD-specific aggregation. This approach derives dynamic consensus models of aggregate growth and architecture, implicating highly influential proteins as new targets to disrupt amyloid accrual in the AD brain.
Chronic acrylamide exposure resulted in dopaminergic neuron loss, neuroinflammation and motor impairment in rats
2022, Toxicology and Applied Pharmacology
Acrylamide (ACR) as a by-product of Maillard reaction is widely present in food. Although ACR is known to exhibit neurotoxicity, most studies about ACR neurotoxicity are currently short-term high-dose providing limited reference value for human exposure. The present study aims to determine the effects of chronic ACR exposure on dopaminergic neurons in rat nigra and the potential mechanism from the perspective of NLRP3 inflammasome-mediated neuroinflammation. The SD rats were maintained on treated drinking water providing dosages of 0, 0.5, or 5 mg/kg/day ACR for 12 months. ACR exposure caused motor dysfunction in rats, which was associated with dopaminergic neuron loss, α-Synuclein (α-Syn) accumulation and decreased brain-derived neurotrophic factor (BDNF) in nigra. ACR activated microglia by increasing Iba-1⁺, Iba-1⁺CD68⁺ positive cells and the percentage of ameboid-shaped ones in rat nigra. ACR markedly upregulated the protein levels of NLRP3 inflammasome constituents NLRP3 and caspase-1 and inflammatory cytokine IL-1β. ACR chronic exposure increased the risk of Parkinson's disease (PD) like dopaminergic neuron depletion in nigra potentially through NLRP3 inflammasome-mediated neuroinflammtion.
Glial cells in Alzheimer's disease: From neuropathological changes to therapeutic implications
2022, Ageing Research Reviews
Alzheimer's disease (AD) is a neurodegenerative disorder that usually develops slowly and progressively worsens over time. Although there has been increasing research interest in AD, its pathogenesis is still not well understood. Although most studies primarily focus on neurons, recent research findings suggest that glial cells (especially microglia and astrocytes) are associated with AD pathogenesis and might provide various possible therapeutic targets. Growing evidence suggests that microglia can provide protection against AD pathogenesis, as microglia with weakened functions and impaired responses to Aβ proteins are linked with elevated AD risk. Interestingly, numerous findings also suggest that microglial activation can be detrimental to neurons. Indeed, microglia can induce synapse loss via the engulfment of synapses, possibly through a complement-dependent process. Furthermore, they can worsen tau pathology and release inflammatory factors that cause neuronal damage directly or through the activation of neurotoxic astrocytes. Astrocytes play a significant role in various cerebral activities. Their impairment can mediate neurodegeneration and ultimately the retraction of synapses, resulting in AD-related cognitive deficits. Deposition of Aβ can result in astrocyte reactivity, which can further lead to neurotoxic effects and elevated secretion of inflammatory mediators and cytokines. Moreover, glial-induced inflammation in AD can exert both beneficial and harmful effects. Understanding the activities of astrocytes and microglia in the regulation of AD pathogenesis would facilitate the development of novel therapies. In this article, we address the implications of microglia and astrocytes in AD pathogenesis. We also discuss the mechanisms of therapeutic agents that exhibit anti-inflammatory effects against AD.
Fighting fire with fire: The immune system might be key in our fight against Alzheimer's disease
2022, Drug Discovery Today
The ultimate cause of Alzheimer’s disease (AD) is still unknown and no disease-modifying treatment exists. Emerging evidence supports the concept that the immune system has a key role in AD pathogenesis. This awareness leads to the idea that specific parts of the immune system must be engaged to ward off the disease. Immunotherapy has dramatically improved the management of several previously untreatable cancers and could hold similar promise as a novel therapy for treating AD. However, before potent immunotherapies can be rationally designed as treatment against AD, we need to fully understand the dynamic interplay between AD and the different parts of our immune system. Accordingly, here we review the most important aspects of both the innate and adaptive immune system in relation to AD pathology.
Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice
2022, Journal of Ethnopharmacology
Citation Excerpt :
Imperative is IL-1β which can additionally initiate its own expression as observed in an increase IL-1β in murine brain after injecting it with human IL-1β (Depino et al., 2005; Shaftel et al., 2007). Literatures have documented that IL-1ra controls the biological action of IL-1β invivo by forestalling the binding of IL-1β to IL-1 type I receptor (IL-1RI) (Sheng et al., 2000; Basu et al., 2002; Liao et al., 2004; Lin et al., 2006). Evidences have proposed a mechanistic link between ROS and IL-1β on the ground that oxidant stress is a specific and primary trigger of IL-1β expression (Min et al., 2003; Viviani et al., 2001; Brabers and Nottet, 2006).
Bacopa floribunda (BF), a locally available plant has been employed traditionally as memory enhancer in Southwestern, Nigeria. It has been utilized in traditional and Ayurvedic medicine as brain tonic for enhancing memory, anti-aging and forestalling series of psychological disorders. However, there is a dearth of scientific information on the mechanism(s) of action of important phytochemicals from BF extract on dementia.
Alzheimer's disease, the commonest form of dementia has been postulated to triple by 2050 as a result of increase in life expectancy. This study therefore assessed and compared the possible mechanism(s) of action of flavonoids and saponins from BF on Amyloid beta (Aβ1-42)-induced dementia in male BALB/c mice.
Eighty (80) healthy BALB/c mice divided into 10 groups (n = 8) were given a single bilateral ICV injection of Aβ1-42 or normal saline. Graded doses of Saponins and flavonoids (50, 100 and 200 mg/kg) were used as treatment for 21 days. Hippocampal homogenates were assayed for the levels of antioxidants, oxidative stress and neuroinflammatory markers. In vitro antioxidant activity of flavonoids and saponins were equally assessed using standard procedures. The extent of microglial activation was quantified through immunohistochemistry procedure.
Aβ1-42 successfully caused a spike in hippocampal levels of MDA, IL1β, TNF-α including MPO levels and invariably decreased antioxidant activities. Likewise an increase in reactive microglia (microgliosis) was observed. However, crude saponins and flavonoids from BF were able to suppress microgliosis, oxidative stress and neuroinflammation induced by Aβ1- 42 and were observed to be more effective at higher doses of saponins (100 mg/kg and 200 mg/kg) and flavonoid (100 mg/kg).
Phytochemicals from BF efficiently exhibited dose dependent alleviation of some symptoms associated with Alzheimer's disease.
Therapeutic strategies for tauopathies and drug repurposing as a potential approach
2022, Biochemical Pharmacology
Tauopathies are neurodegenerative diseases characterized by the deposition of abnormal tau in the brain. To date, there are no disease-modifying therapies approved by the U.S. Food and Drug Administration (US FDA) for the treatment of tauopathies. In the past decades, extensive efforts have been provided to develop disease-modifying therapies to treat tauopathies. Specifically, exploring existing drugs with the intent of repurposing for the treatment of tauopathies affords a reasonable alternative to discover potent drugs for treating these formidable diseases. Drug repurposing will not only reduce formulation and development stage effort and cost but will also take a key advantage of the established toxicological studies, which is one of the main causes of clinical trial failure of new molecules. In this review, we provide an overview of the current treatment strategies for tauopathies and the recent progress in drug repurposing as an alternative approach to treat tauopathies.

View all citing articles on Scopus

¹: To whom correspondence and reprint requests should be addressed at 4300 W. 7th Street, Little Rock, AR 72205. Fax: (501) 257-5556. E-mail: [email protected].

View full text

Article preview

Experimental Neurology

Abstract

References (19)

Tau mRNA isoforms following sciatic nerve axotomy with and without regeneration

Mol. Brain Res.

Senescence-accelerated overexpression of S100β in brain of SAMP6 mice

Neurobiol. Aging

Inactivation of a redox-sensitive protein phosphatase during the early events of tumor necrosis factor/interleukin-1 signal transduction

J. Biol. Chem.

Hyperphosphorylation of tau in PHF

Neurobiol. Aging

Glial cytokines in Alzheimer's disease. Review and pathogenic implications

Hum. Pathol.

Towards an understanding of the signal transduction pathways for interleukin 1

Biochim. Biophys. Acta

Functions and mechanisms of interleukin 1 in the brain

Trends Pharmacol. Sci.

In vivo and in vitro evidence supporting a role for the inflammatory cytokine interleukin-1 as a driving force in Alzheimer pathogenesis

Neurobiol. Aging

Plaque biogenesis in brain aging and Alzheimer's disease. I. Progressive changes in phosphorylation states of paired helical filaments and neurofilaments

Brain Res.

Cited by (130)

Alzheimer's-specific brain amyloid interactome: Neural-network analysis of intra-aggregate crosslinking identifies novel drug targets

Chronic acrylamide exposure resulted in dopaminergic neuron loss, neuroinflammation and motor impairment in rats

Glial cells in Alzheimer's disease: From neuropathological changes to therapeutic implications

Fighting fire with fire: The immune system might be key in our fight against Alzheimer's disease

Saponins and flavonoids from Bacopa floribunda plant extract exhibit antioxidant and anti-inflammatory effects on amyloid beta 1-42-induced Alzheimer's disease in BALB/c mice

Therapeutic strategies for tauopathies and drug repurposing as a potential approach

Brief CommunicationInterleukin-1 Promotes Expression and Phosphorylation of Neurofilament and tau Proteins in Vivo

Abstract

Mol. Brain Res.

Neurobiol. Aging

J. Biol. Chem.

Neurobiol. Aging

Hum. Pathol.

Biochim. Biophys. Acta

Trends Pharmacol. Sci.

Neurobiol. Aging

Brain Res.

Brief Communication
Interleukin-1 Promotes Expression and Phosphorylation of Neurofilament and tau Proteins in Vivo