Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

Maiti, Panchanan; Rossignol, Julien; Dunbar, Gary

doi:10.4172/2161-0460.1000299

Cited by 14 publications

(13 citation statements)

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“…Curcumin have beneficial effects on AD including antioxidative, anti-Aβ aggregation, and inhibition of acetylcholinesterase, β-secretase, and Aβ-induced inflammation in vitro as well as inhibition of tau phosphorylation and Aβ oligomerization in the brain in vivo ( 12 , 18 ). One of the key steps in Aβ generation is cleavage of APP by β-site APP-cleaving enzyme 1 (BACE-1) and β-secretase.…”

Section: Discussionmentioning

confidence: 99%

“…Lin et al found curcumin almost completely suppressed the up-expression of APP and BACE-1 mRNA levels ( 26 ), indicating that curcumin exerts effects on APP processing. Maiti et al ( 18 ) suggested that curcumin or solid lipid curcumin particles treatment could increase the levels of LC3A/B-II and Beclin-1, indicating that maintenance or restoration of heat shock proteins and regulation of autophagy–lysosomal pathways by curcumin may provide a promising strategy to degrade Aβ-aggregates from neurons in the AD brain. To some extent, our study is consistent with this previous study, showing that the markers of the autophagy–lysosomal system (Beclin, LC3, and LAMP-1) were downregulated after curcumin use in Aβ1-42-treated HT-22 cells.…”

Section: Discussionmentioning

confidence: 99%

“…A final concentration of 10 μM was used in our study. Curcumin preparation was performed as previously described ( 18 ). In brief, the stock curcumin were dissolved in methanol and then diluted in the DMEM or MEM (methanol was <1%), before being added to the Petri dish containing the cells.…”

Section: Methodsmentioning

confidence: 99%

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RETRACTED: Curcumin Exerts Effects on the Pathophysiology of Alzheimer’s Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression

et al. 2017

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BackgroundTo validate our speculation that curcumin may ameliorate Alzheimer’s disease (AD) pathogenesis by regulating PI(3,5)P2 and transient receptor potential mucolipin-1 (TRPML1) expression levels.MethodsWe developed an animal model presenting AD by APP/PS1 transgenes. The mouse clonal hippocampal neuronal cell line HT-22 was treated with amyloid-β1-42 (Aβ1-42). Curcumin was administrated both in vivo and in vitro. MTS assay was used to detect cell viability, and the lysosomal [Ca2+] ion concentration was detected. The number of autophagosomes was detected by the transmission electron microscopic examination. Illumina RNA-seq was used to analyze the different expression patterns between Aβ1-42-treated cells without and with curcumin treatment. The protein level was analyzed by the Western blotting analysis. PI(3,5)P2 or TRPML1 was knocked down in HT-22 cells or in APP/PS1 transgenic mice. Morris water maze and recognition task were performed to trace the cognitive ability.ResultsCurcumin increased cell viability, decreased the number of autophagosomes, and increased lysosomal Ca2+ levels in Aβ1-42-treated HT-22 cells. Sequencing analysis identified TRPLML1 as the most significantly upregulated gene after curcumin treatment. Western blotting results also showed that TRPML1 was upregulated and mTOR/S6K signaling pathway was activated and markers of the autophagy–lysosomal system were downregulated after curcumin use in Aβ1-42-treated HT-22 cells. Knockdown of PI (3,5)P2 or TRPML1 increased the protein levels of markers of the autophagy–lysosomal system after curcumin use in Aβ1-42-treated HT-22 cells, inhibited mTOR/S6K signaling pathway, increased the protein levels of markers of the autophagy–lysosomal system after curcumin use in APP/PS1 mice. Besides, knockdown of PI(3,5)P2 or TRPML1 reversed the protective role of curcumin on memory and recognition impairments in mice with APP/PS1 transgenes.ConclusionTo some extent, it suggested that the effects of curcumin on AD pathogenesis were, at least partially, associated with PI(3,5)P2 and TRPML1 expression levels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Curcumin Exerts Effects on the Pathophysiology of Alzheimer’s Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression

et al. 2017

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“…In contrast, ATG inhibition abrogates the beneficial effects of curcumin [ 31 ]. Again, anti-fibrillogenic effects of curcumin in counteracting the aggregation of proteins such as tau, amyloid-beta, and α-synuclein, which occur in NDDs, rely on the very same mTOR inhibition, which in turn produces ATG activation [ 33 , 34 , 35 ]. For instance, treatment with curcumin reduces the pathological accumulation of mutated (A53T) α-synuclein in dopamine (DA)-containing SH-SY5Y cells through downregulation of the mTOR/p70S6K pathway and thus ATG recovery [ 36 ].…”

Section: Pleiotropic Effects Of Curcumin In the Cns: From Neuropromentioning

confidence: 99%

The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

et al. 2020

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The present review focuses on the multi-faceted effects of curcumin on the neurobiology glioblastoma multiforme (GBM), with a special emphasis on autophagy (ATG)-dependent molecular pathways activated by such a natural polyphenol. This is consistent with the effects of curcumin in a variety of experimental models of neurodegeneration, where the molecular events partially overlap with GBM. In fact, curcumin broadly affects various signaling pathways, which are similarly affected in cell degeneration and cell differentiation. The antitumoral effects of curcumin include growth inhibition, cell cycle arrest, anti-migration and anti-invasion, as well as chemo- and radio-sensitizing activity. Remarkably, most of these effects rely on mammalian target of rapamycin (mTOR)-dependent ATG induction. In addition, curcumin targets undifferentiated and highly tumorigenic GBM cancer stem cells (GSCs). When rescuing ATG with curcumin, the tumorigenic feature of GSCs is suppressed, thus counteracting GBM establishment and growth. It is noteworthy that targeting GSCs may also help overcome therapeutic resistance and reduce tumor relapse, which may lead to a significant improvement of GBM prognosis. The present review focuses on the multi-faceted effects of curcumin on GBM neurobiology, which represents an extension to its neuroprotective efficacy.

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“…Through the induction of autophagy, quercetin antagonizes Aβ-induced neurotoxicity [ 222 ], while quercetin nanoparticles promote the fusion of autophagosomes and lysosomes, which is associated with enhanced clearance of Aβ, and cytoprotection from Aβ-induced toxicity [ 51 ]. Similar to quercetin, curcumin exerts anti-fibrillogenic effects and counteracts the aggregation of tau and Aβ through mTOR-dependent autophagy activation [ 223 , 224 ]. Similar effects in AD mice models are provided by berberine, which reduces hyperphosphorylation of tau and promotes its clearance through autophagy induction via Akt/GSK3-β and PI3K/Beclin-1 pathways [ 118 ].…”

Section: Phytochemicals and Proteostasismentioning

confidence: 99%

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

et al. 2020

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Wide experimental evidence has been provided in the last decade concerning the neuroprotective effects of phytochemicals in a variety of neurodegenerative disorders. Generally, the neuroprotective effects of bioactive compounds belonging to different phytochemical classes are attributed to antioxidant, anti-aggregation, and anti-inflammatory activity along with the restoration of mitochondrial homeostasis and targeting alterations of cell-clearing systems. Far from being independent, these multi-target effects represent interconnected events that are commonly implicated in the pathogenesis of most neurodegenerative diseases, independently of etiology, nosography, and the specific misfolded proteins being involved. Nonetheless, the increasing amount of data applying to a variety of neurodegenerative disorders joined with the multiple effects exerted by the wide variety of plant-derived neuroprotective agents may rather confound the reader. The present review is an attempt to provide a general guideline about the most relevant mechanisms through which naturally occurring agents may counteract neurodegeneration. With such an aim, we focus on some popular phytochemical classes and bioactive compounds as representative examples to design a sort of main highway aimed at deciphering the most relevant protective mechanisms which make phytochemicals potentially useful in counteracting neurodegeneration. In this frame, we emphasize the potential role of the cell-clearing machinery as a kernel in the antioxidant, anti-aggregation, anti-inflammatory, and mitochondrial protecting effects of phytochemicals.

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Curcumin Modulates Molecular Chaperones and Autophagy-Lysosomal Pathways In Vitro after Exposure to Aβ42

Cited by 14 publications

References 58 publications

RETRACTED: Curcumin Exerts Effects on the Pathophysiology of Alzheimer’s Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression

RETRACTED: Curcumin Exerts Effects on the Pathophysiology of Alzheimer’s Disease by Regulating PI(3,5)P2 and Transient Receptor Potential Mucolipin-1 Expression

The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

Merging the Multi-Target Effects of Phytochemicals in Neurodegeneration: From Oxidative Stress to Protein Aggregation and Inflammation

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