Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer’s Disease

Lakey-Beitia, Johant; González, Yisett; Doens, Deborah; Stephens, David E.; Santamarı́a, Ricardo; Murillo, Enrique G.; Gutiérrez, Marcelino; Fernández, Patricia L.; Rao, K. S.; Larionov, Oleg V.; Durant-Archibold, Armando A.

doi:10.3233/jad-170071

Cited by 40 publications

(36 citation statements)

References 18 publications

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“…This finding provides the basis for the development of a high-resolution noninvasive optical-imaging technique for detecting Aβ plaques in the retina, allowing the early diagnosis and follow up of AD (Koronyo-Hamaoui et al, 2011; Kayabasi et al, 2014). In addition, curcumin has been revealed to be a novel agent for treating AD through different neuroprotective mechanisms, such as inhibition of Aβ aggregation and decrease in neuroinflammation (Maiti and Dunbar, 2016; Lakey-Beitia et al, 2017). …”

Section: Neurodegenerative Diseases and The Eyementioning

confidence: 99%

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

Ramírez

Hoz

Salobrar‐García

et al. 2017

Front. Aging Neurosci.

379

341

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Microglia, the immunocompetent cells of the central nervous system (CNS), act as neuropathology sensors and are neuroprotective under physiological conditions. Microglia react to injury and degeneration with immune-phenotypic and morphological changes, proliferation, migration, and inflammatory cytokine production. An uncontrolled microglial response secondary to sustained CNS damage can put neuronal survival at risk due to excessive inflammation. A neuroinflammatory response is considered among the etiological factors of the major aged-related neurodegenerative diseases of the CNS, and microglial cells are key players in these neurodegenerative lesions. The retina is an extension of the brain and therefore the inflammatory response in the brain can occur in the retina. The brain and retina are affected in several neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), and glaucoma. AD is an age-related neurodegeneration of the CNS characterized by neuronal and synaptic loss in the cerebral cortex, resulting in cognitive deficit and dementia. The extracellular deposits of beta-amyloid (Aβ) and intraneuronal accumulations of hyperphosphorylated tau protein (pTau) are the hallmarks of this disease. These deposits are also found in the retina and optic nerve. PD is a neurodegenerative locomotor disorder with the progressive loss of dopaminergic neurons in the substantia nigra. This is accompanied by Lewy body inclusion composed of α-synuclein (α-syn) aggregates. PD also involves retinal dopaminergic cell degeneration. Glaucoma is a multifactorial neurodegenerative disease of the optic nerve, characterized by retinal ganglion cell loss. In this pathology, deposition of Aβ, synuclein, and pTau has also been detected in retina. These neurodegenerative diseases share a common pathogenic mechanism, the neuroinflammation, in which microglia play an important role. Microglial activation has been reported in AD, PD, and glaucoma in relation to protein aggregates and degenerated neurons. The activated microglia can release pro-inflammatory cytokines which can aggravate and propagate neuroinflammation, thereby degenerating neurons and impairing brain as well as retinal function. The aim of the present review is to describe the contribution in retina to microglial-mediated neuroinflammation in AD, PD, and glaucomatous neurodegeneration.

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Section: Neurodegenerative Diseases and The Eyementioning

confidence: 99%

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

Ramírez

Hoz

Salobrar‐García

et al. 2017

Front. Aging Neurosci.

379

341

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“…Lakey-Beitia and colleagues (2017) [65] synthesized new curcumin derivatives and studied anti-Aβ aggregation and anti-inflammatory activities in AD. Nine curcumin derivatives were synthesized by etherification and esterification of the aromatic region.…”

Section: Curcumin and Its Derivatives Design And Synthesismentioning

confidence: 99%

“…Mono-functionalized curcumin derivatives showed better bioactivity than difunctionalized compounds. Moreover, the presence of bulky groups in the chemical structure of curcumin derivatives decreased bioactivity [65]. …”

Section: Curcumin and Its Derivatives Design And Synthesismentioning

confidence: 99%

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Reddy

Mańczak

Yin

et al. 2018

JAD

287

138

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The purpose of our article is to assess the current understanding of Indian spice ‘Curcumin’ against amyloid-β (Aβ)-induced toxicity in Alzheimer’s disease (AD) pathogenesis. Natural products, such as ginger, curcumin and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, anti-oxidant, anti-arthritis, pro-healing and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells and protect neurons from various toxic insults of aging and amyloid-β in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin’s bioavailability and urgent need for new formulation to increase its brain levels to treat patients with AD.

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“…Meanwhile, there is also not enough data to support that preventive or potential treatment measures could reduce the incidence of neuropathic pain in diabetic patients 10 . Curcumin is a natural product that has extensive biological activities and cellular mechanisms, while plays an effective role in the treatment of diseases such as Alzheimer's disease, cancers, diabetes, DPN and inflammation [11][12][13][14] . Cocorocchio et al 15 attests that curcumin can act on cells in an acute manner, reduce cell growth and slow down multicellular development.…”

Section: ■ Introductionmentioning

confidence: 99%

A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

Cao

Zhang

et al. 2018

Acta Cir. Bras.

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A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1 1 8-Experimental SurgeryActa Cir Bras. 2018;33(6):533-541 AbstractPurpose: To investigate the specific molecular mechanisms and effects of curcumin derivative J147 on diabetic peripheral neuropathy (DPN). Methods: We constructed streptozotocin (STZ)-induced DPN rat models to detected mechanical withdrawal threshold (MWT) in vivo using Von Frey filaments. In vitro, we measured cell viability and apoptosis, adenosine 5'-monophosphate-activated protein kinase (AMPK) and transient receptor potential A1 (TRPA1) expression using MTT, flow cytometry, qRT-PCR and western blot. Then, TRPA1 expression level and calcium reaction level were assessed in agonist AICAR treated RSC96cells. Results:The results showed that J147reduced MWT in vivo, increased the mRNA and protein level of AMPK, reduced TRPA1 expression and calcium reaction level in AITCR treated RSC96 cells, and had no obvious effect on cell viability and apoptosis. 18 reports that J147 improves the depression-like behavior in mouse models caused by chronic stress, and its mechanism may involve the regulation of cAMP/pCREB/ BDNF pathway.Due to curcumin can relieve diabetic peripheral neuropathic pain 14 , we aimed to investigate the specific molecular mechanisms and effects of J147 on DPN through the establishment of DPN rat models, cell viability and apoptosis assay in this study. ■ Methods DPN rat modelsEthical Guidelines were approved by the Ethical Committee of Shanxi University of Traditional Chinese Medicine.The 30 adult male SPF rats (weighing 200 ± 20g) were obtained from Institute of Laboratory Animal Science, Chinese Academy of Medical Science (Beijing, China). They were housed in stainless steel squirrel cages with food and water available ad libitum. The breeding room was kept at 20°C, 70% humidity and 12 h of light.SPF rats were weighed after fasting for 12 h, and streptozotocin(STZ) solution (Solarbio, Beijing, China) was injected intraperitoneally at 50 mg/kg weight. After 4 h of injection, the rats resumed their diet ■ IntroductionDiabetic peripheral neuropathy (DPN) is one of the major disability factors and the most common chronic neurological complications in diabetes 1 . The clinical manifestations of this disease are distal symmetric pain with paresthesia, like numbness, ant walking, insect crawling, fever, electric shock, and motor neurological disorders 2,3 .Further, severe DPN patients may develop lower extremity arthropathy and ulcers 2 . In addition, there will be DPN in 30-50% diabetic patients by 2025 according to the prediction from WHO 4 . Therefore, in order to ameliorate the patient's clinical symptoms and control the development of DPN, the comprehensive treatments are used, such as control of blood glucose, oral Duloxetine and Pregabalin, interventional therapy and surgical treatment [5][6][7][8] . Regardless, the exact pathogenesis of DPN is not fully understood until now. ...

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Assessment of Novel Curcumin Derivatives as Potent Inhibitors of Inflammation and Amyloid-β Aggregation in Alzheimer’s Disease

Cited by 40 publications

References 18 publications

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

The Role of Microglia in Retinal Neurodegeneration: Alzheimer's Disease, Parkinson, and Glaucoma

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1

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