scholarly journals Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

2017 ◽  
Vol 44 (2) ◽  
pp. 479-493 ◽  
Author(s):  
Yanhe Wang ◽  
Zhiyuan Yin ◽  
Lixiong Gao ◽  
Dayu Sun ◽  
Xisu Hu ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Neurodegenerative Disorders ◽  
Visual Function ◽  
Underlying Mechanism ◽  
Microglia Activation ◽  
Swine Model ◽  
Behavioral Tests ◽  
Curcumin Treatment ◽  
Neuroprotective Effects ◽  
Bv2 Microglial Cells

Background/Aims: Retinitis pigmentosa (RP) is characterized by degeneration of photoreceptors, and there are currently no effective treatments for this disease. However, curcumin has shown neuroprotectant efficacy in a RP rat and swine model, and thus, may have neuroprotective effects in this disease. Methods: Immunofluorescence staining, electroretinogram recordings, and behavioral tests were used to analyze the effects of curcumin and the underlying mechanism in retinal degeneration 1 (rd1) mice. Results: The number of apoptotic cells in the retina of rd1 mice at postnatal day 14 significantly decreased with curcumin treatment and visual function was improved. The activation of microglia and secretion of chemokines and matrix metalloproteinases in the retina were inhibited by curcumin. These effects were also observed in a co-culture of BV2 microglial cells and retina-derived 661W cells. Conclusions: Curcumin delayed retinal degeneration by suppressing microglia activation in the retina of rd1 mice. Thus, it may be an effective treatment for neurodegenerative disorders such as RP.

scholarly journals trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Fu ◽  
Pin Yang ◽  
Yang Zhao ◽  
Liqing Zhang ◽  
Zhangang Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Microglial Cells ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Parkinson’S Diseases ◽  
Cox 2 ◽  
Bv2 Microglial Cells

Background.Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled.trans-cinnamaldehyde (TCA) isolated from the stem bark ofCinnamomum cassiapossesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells.Results.To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1βand recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects.Conclusions.Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

scholarly journals Constituents of Gastrodia elata and Their Neuroprotective Effects in HT22 Hippocampal Neuronal, R28 Retinal Cells, and BV2 Microglial Cells

Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1051
Author(s):  
Hye Mi Kim ◽  
Jaeyoung Kwon ◽  
Kyerim Lee ◽  
Jae Wook Lee ◽  
Dae Sik Jang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Spectroscopic Data ◽  
Neuronal Cells ◽  
Mass Spectrometry Data ◽  
Microglial Cells ◽  
Nitric Oxide Production ◽  
Gastrodia Elata ◽  
Neuroprotective Effects ◽  
Retinal Cells ◽  
Bv2 Microglial Cells

Gastrodia elata is widely used in traditional medicine and contains various types of metabolites with pharmacological activity. In the course of searching for neuroprotective molecules associated with the potential of G. elata in the treatment of neurodegenerative disorders, two new phenolic compounds (1 and 2) and a new tripeptide (3), together with 16 known compounds (4–19), were isolated from the rhizomes of G. elata. The structures of the compounds were determined by the interpretation of spectroscopic data, including nuclear magnetic resonance and mass spectrometry data. All obtained compounds were assessed for their ability to protect neuronal cells against neurotoxicity and neuroinflammation. Of these, 4 and 5 were found to possess moderate activities in HT22 hippocampal neuronal cells, whereas 2, 6, and 7 showed weak activities in R28 retinal cells. Additionally, compound 9 showed moderate inhibitory activity on lipopolysaccharide-induced nitric oxide production in BV2 microglial cells.

scholarly journals Microglia activation in a model of retinal degeneration and TUDCA neuroprotective effects

2014 ◽  
Vol 11 (1) ◽  
Author(s):  
Agustina Noailles ◽  
Laura Fernández-Sánchez ◽  
Pedro Lax ◽  
Nicolás Cuenca
Keyword(s):  
Retinal Degeneration ◽  
Microglia Activation ◽  
Neuroprotective Effects

scholarly journals Benefits under the Sea: The Role of Marine Compounds in Neurodegenerative Disorders

Marine Drugs ◽  
2021 ◽  
Vol 19 (1) ◽  
pp. 24
Author(s):  
Mariano Catanesi ◽  
Giulia Caioni ◽  
Vanessa Castelli ◽  
Elisabetta Benedetti ◽  
Michele d’Angelo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorders ◽  
Extreme Temperature ◽  
Bioactive Molecules ◽  
Neuroprotective Effects ◽  
Physical Conditions ◽  
Adjuvant Therapies ◽  
Marine Habitats ◽  
Marine Compounds

Marine habitats offer a rich reservoir of new bioactive compounds with great pharmaceutical potential; the variety of these molecules is unique, and its production is favored by the chemical and physical conditions of the sea. It is known that marine organisms can synthesize bioactive molecules to survive from atypical environmental conditions, such as oxidative stress, photodynamic damage, and extreme temperature. Recent evidence proposed a beneficial role of these compounds for human health. In particular, xanthines, bryostatin, and 11-dehydrosinulariolide displayed encouraging neuroprotective effects in neurodegenerative disorders. This review will focus on the most promising marine drugs’ neuroprotective potential for neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. We will describe these marine compounds’ potential as adjuvant therapies for neurodegenerative diseases, based on their antioxidant, anti-inflammatory, and anti-apoptotic properties.

scholarly journals Anti–Na+/K+-ATPase immunotherapy ameliorates α-synuclein pathology through activation of Na+/K+-ATPase α1–dependent autophagy

2021 ◽  
Vol 7 (5) ◽  
pp. eabc5062
Author(s):  
Lei Cao ◽  
Siping Xiong ◽  
Zhiyuan Wu ◽  
Lei Ding ◽  
Yebo Zhou ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tyrosine Hydroxylase ◽  
Neurodegenerative Diseases ◽  
Motor Function ◽  
Therapeutic Strategy ◽  
Underlying Mechanism ◽  
Behavioral Tests ◽  
Behavioral Deficits ◽  
Cellular Homeostasis ◽  
Beneficial Effects

Na+/K+-ATPase (NKA) plays important roles in maintaining cellular homeostasis. Conversely, reduced NKA activity has been reported in aging and neurodegenerative diseases. However, little is known about the function of NKA in the pathogenesis of Parkinson’s disease (PD). Here, we report that reduction of NKA activity in NKAα1+/− mice aggravates α-synuclein–induced pathology, including a reduction in tyrosine hydroxylase (TH) and deficits in behavioral tests for memory, learning, and motor function. To reverse this effect, we generated an NKA-stabilizing monoclonal antibody, DR5-12D, against the DR region (897DVEDSYGQQWTYEQR911) of the NKAα1 subunit. We demonstrate that DR5-12D can ameliorate α-synuclein–induced TH loss and behavioral deficits by accelerating α-synuclein degradation in neurons. The underlying mechanism for the beneficial effects of DR5-12D involves activation of NKAα1-dependent autophagy via increased AMPK/mTOR/ULK1 pathway signaling. Cumulatively, this work demonstrates that NKA activity is neuroprotective and that pharmacological activation of this pathway represents a new therapeutic strategy for PD.

Astrocyte Reactivity in Alzheimer’s Disease: Therapeutic Opportunities to Promote Repair

2021 ◽  
Vol 18 ◽  
Author(s):  
Nazanin Mirzaei ◽  
Nicola Davis ◽  
Tsz Wing Chau ◽  
Magdalena Sastre
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mouse Models ◽  
Neurodegenerative Disorders ◽  
Amyloid Β ◽  
Neuroprotective Effects ◽  
Synaptic Density ◽  
Inflammatory Profile

: Astrocytes are fast climbing the ladder of importance in neurodegenerative disorders, particularly in Alzheimer’s disease (AD), with the prominent presence of reactive astrocytes sur- rounding amyloid β- plaques, together with activated microglia. Reactive astrogliosis, implying morphological and molecular transformations in astrocytes, seems to precede neurodegeneration, suggesting a role in the development of the disease. Single-cell transcriptomics has recently demon- strated that astrocytes from AD brains are different from “normal” healthy astrocytes, showing dys- regulations in areas such as neurotransmitter recycling, including glutamate and GABA, and im- paired homeostatic functions. However, recent data suggest that the ablation of astrocytes in mouse models of amyloidosis results in an increase in amyloid pathology as well as in the inflammatory profile and reduced synaptic density, indicating that astrocytes mediate neuroprotective effects. The idea that interventions targeting astrocytes may have great potential for AD has therefore emerged, supported by a range of drugs and stem cell transplantation studies that have successfully shown a therapeutic effect in mouse models of AD. In this article, we review the latest reports on the role and profile of astrocytes in AD brains and how manipulation of astrocytes in animal mod- els has paved the way for the use of treatments enhancing astrocytic function as future therapeutic avenues for AD.

scholarly journals Antisense oligonucleotides targeting mutant Ataxin-7 restore visual function in a mouse model of spinocerebellar ataxia type 7

2018 ◽  
Vol 10 (465) ◽  
pp. eaap8677 ◽  
Author(s):  
Chenchen Niu ◽  
Thazah P. Prakash ◽  
Aneeza Kim ◽  
John L. Quach ◽  
Laryssa A. Huryn ◽  
...  
Keyword(s):  
Retinal Degeneration ◽  
Spinocerebellar Ataxia ◽  
Visual Function ◽  
Antisense Oligonucleotides ◽  
Neurodegenerative Disorder ◽  
Retinal Disease ◽  
Fundus Photography ◽  
Spinocerebellar Ataxia Type ◽  
Autofluorescence Imaging ◽  
Spinocerebellar Ataxia Type 7

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by cerebellar and retinal degeneration, and is caused by a CAG-polyglutamine repeat expansion in the ATAXIN-7 gene. Patients with SCA7 develop progressive cone-rod dystrophy, typically resulting in blindness. Antisense oligonucleotides (ASOs) are single-stranded chemically modified nucleic acids designed to mediate the destruction, prevent the translation, or modify the processing of targeted RNAs. Here, we evaluated ASOs as treatments for SCA7 retinal degeneration in representative mouse models of the disease after injection into the vitreous humor of the eye. Using Ataxin-7 aggregation, visual function, retinal histopathology, gene expression, and epigenetic dysregulation as outcome measures, we found that ASO-mediated Ataxin-7 knockdown yielded improvements in treated SCA7 mice. In SCA7 mice with retinal disease, intravitreal injection of Ataxin-7 ASOs also improved visual function despite initiating treatment after symptom onset. Using color fundus photography and autofluorescence imaging, we also determined the nature of retinal degeneration in human SCA7 patients. We observed variable disease severity and cataloged rapidly progressive retinal degeneration. Given the accessibility of neural retina, availability of objective, quantitative readouts for monitoring therapeutic response, and the rapid disease progression in SCA7, ASOs targeting ATAXIN-7 might represent a viable treatment for SCA7 retinal degeneration.

scholarly journals Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders

Medicines ◽  
2018 ◽  
Vol 5 (4) ◽  
pp. 126 ◽  
Author(s):  
Miora Rakotoarisoa ◽  
Angelina Angelova
Keyword(s):  
Neurodegenerative Disorders ◽  
Liquid Crystalline ◽  
Water Solubility ◽  
Neuronal Loss ◽  
Drug Solubility ◽  
Neuroprotective Effects ◽  
Slowing Down ◽  
Combination Treatments ◽  
Physico Chemical ◽  
Lateral Sclerosis

Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid- and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis (ALS).

Divergent Phenotypes of Vision and Accessory Visual Function in Mice with Visual Cycle Dysfunction (Rpe65rd12) or Retinal Degeneration (rd/rd)

2008 ◽  
Vol 49 (6) ◽  
pp. 2737 ◽  
Author(s):  
Stewart Thompson ◽  
Robert F. Mullins ◽  
Alisdair R. Philp ◽  
Edwin M. Stone ◽  
N. Mrosovsky
Keyword(s):  
Retinal Degeneration ◽  
Visual Function ◽  
Visual Cycle

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

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