Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice

Sabogal‐Guáqueta, Angélica Maria; Osorio, Edison; Cardona‐Gómez, Gloria Patricia

doi:10.1016/j.neuropharm.2015.11.002

Cited by 114 publications

(88 citation statements)

References 47 publications

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“…Moreover, Zheng et al reported that linalool exerts anti-inflammatory effects through the induction of Nrf2 nuclear translocation and the expression of HO-1. [154] An in vivo study performed on aged mice and transgenic model of AD (3xTg-AD) showed that a chronic treatment with linalool induced a significant reduction of A-deposition, and in the levels of the pro-inflammatory markers p38 MAPK, NOS2, COX2 and IL-1β [155,156]. All these data suggest that linalool is able to reverse the histopathological hallmarks of AD and to restore cognitive functions via an antiinflammatory effect.…”

Section: Nature-based Ligands As a Source To Design Multitarget Drugsmentioning

confidence: 98%

Oxidative Stress, Mitochondrial Abnormalities and Proteins Deposition: Multitarget Approaches in Alzheimer's Disease

Nesi

Sestito

Digiacomo

et al. 2017

CTMC

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Alzheimer Diseases (AD) is a multifactorial pathology characterized by a complex etiology. The hallmarks of AD, such as Aβ deposits in senile plaque and Neurofibrillary Tangles (NFT), are strongly intertwined with Reactive Oxygen Species (ROS) production and oxidative stress (OS), which are considered the common effectors of the cascade of degenerative events. An increasing body of evidence reveals that both mitochondrial abnormalities and metal accumulations synergistically act as major producers of ROS, thus contributing to neuronal toxicity. Consequently, the detrimental role of ROS production together with the neurodegenerative events involved in AD has been widely investigated as new potential therapeutic strategies. This review will concisely summarize the link between OS and the hallmarks of AD, emphasizing on their strong correlation with neurodegenerative events and elucidating the pivotal role of ROS in AD pathology. Furthermore, through this review, we will provide a short account of some of the efforts, challenges and opportunities in developing multitarget drugs by addressing ROS production, metal accumulation and protein depositions.

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Section: Nature-based Ligands As a Source To Design Multitarget Drugsmentioning

confidence: 98%

Oxidative Stress, Mitochondrial Abnormalities and Proteins Deposition: Multitarget Approaches in Alzheimer's Disease

Nesi

Sestito

Digiacomo

et al. 2017

CTMC

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“…Six of the studies in the review examined the use of linalool compounds in the management of pro-inflammatory cytokines (Table 2). Deepa and Anuradha (Deepa and Venkatraman Anuradha, 2013); Quintans-Júnior et al , Wu et al (Wu et al, 2014), ; Sabogal-Guaqueta et al (Sabogal-Guáqueta et al, 2016) revealed that 10 to 40 mg/kg of linalool taken orally reduced the proinflammatory cytokines TNF-α, IL-1β, IL-6, which had been increased by different inflammatory inducers. Furthermore, 25 mg/kg (p.o.)…”

Section: Acyclic Monoterpenesmentioning

confidence: 99%

Monoterpenes modulating cytokines - A review

Quintans

Saravanan

Heimfarth

et al. 2019

Food and Chemical Toxicology

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Inflammatory response can be driven by cytokine production and is a pivotal target in the management of inflammatory diseases. Monoterpenes have shown that promising profile as agents which reduce the inflammatory process and also modulate the key chemical mediators of inflammation, such as pro and anti-inflammatory cytokines. The main interest focused on monoterpenes were to develop the analgesic and anti-inflammatory drugs. In this review, we summarized current knowledge on monoterpenes that produce anti-inflammatory effects by modulating the release of cytokines, as well as suggesting that which monoterpenoid molecules may be most effective in the treatment of inflammatory disease. Several different inflammatory markers were evaluated as a target of monoterpenes. The proinflammatory and antiinflammatory cytokines were found TNF-α, IL-1β, IL-2, IL-5, IL-4, IL-6, IL-8, IL-10, IL-12 IL-13, IL-17A, IFNγ, TGF-β1 and IFN-γ. Our review found evidence that NF-κB and MAPK signaling are important pathways for the anti-inflammatory action of monoterpenes. We found 24 monoterpenes that modulate the production of cytokines, which appears to be the major pharmacological mechanism these compounds possess in relation to the attenuation of inflammatory response. Despite the compelling evidence supporting the anti-inflammatory effect of monoterpenes, further studies are necessary to fully explore their potential as anti-inflammatory compounds.

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“…In addition, natural products are considered as a source of potential molecules in the field of neuroprotection (Lara-Guzman et al, 2012; Ho et al, 2013; Sumi et al, 2013; Dong et al, 2014). Therefore, in order to find pharmacological alternatives for a more agile translation to humans, a systemic administration during 3 months in a late stage of the AD mice model has been evaluated, using various natural products as flavonoids by intraperitoneal administration and monoterpenes by oral administration, which surpresively reduced the β-amyloidosis, tauopathy, cognitive disorder and anxiety present in old triple transgenic mice model of AD (Sabogal-Guáqueta et al, 2015, 2016), which could be useful in different kind of neurodegenerative environment and different advanced stages with proinflammatory markers and synaptic deterioration as VCID. Bioavailability analysis and scaling the production will increase the possibility to develop a clinical trial from South America.…”

Section: Preclinical Studies and Molecular Targetsmentioning

confidence: 99%

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

Cardona‐Gómez

Lopera

2016

Front. Aging Neurosci.

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Latin-American people with dementia will increase to an astounding 368% in 2050, higher than USA and Europe. In addition, to sporadic dementia type like Alzheimer, and vascular dementia (VaD) progression after Cerebrovascular disease is also found. These incidences are increased in Colombia by specific populations affected with pure Neurodegenerative and VaDs like Autosomical Dominant familial Alzheimer’s disease (AD) and Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). In spite of the enormous human effort with and economical effort and investment costs, neither sporadic nor genetic kinds of dementia progression have been prevented or blocked yet. Currently, there exist several animal models that partially solve the understanding of the neurodegenerative etiopathogenesis and its treatment. However, when the potential therapies are translated to humans, those do not work or present a limited action. Main difficulties are the diverse comorbility associated to the cause and/or several affected brain regions, reducing the efficacy of some therapies which are limited to a tissue-specific action or modulating a kind of neurotransmission. Global investigation suggests that a general prevention could be achieved with the improvement in the quality of lifestyle, including healthy diet, physical and mental activity, and avoiding mechanical or chemical pro-inflammatory events in an early stage in the most of non-communicable diseases. In this review article, we present some molecular targets and preclinical studies in animal models to propose strategies that could be useful in a future translation to prevent or block neurodegeneration: one is gene therapy; silencing pathogenic genes in critical brain areas where excitotoxicity arise and spread. Another is to take advantage of the natural source and its wide biodiversity of natural products that are capable of identifying, by the blocking and prevention of neurodegeneration. On the other side, the casuistic of pure dementias in the Latin-American region gives an exceptional opportunity to understand the pathogenesis in these human populations. Further, this is in support of the basic and clinical researchers working on an interaction for a better understanding and medical care of mixed dementias, which have more complex factors than pure ones. However, to promote the translation of any therapeutical alternative is necessary to clarify the normative and the protocols for developing clinical trials with original candidates or work upon strategies proposed from South-American countries.

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Linalool reverses neuropathological and behavioral impairments in old triple transgenic Alzheimer's mice

Cited by 114 publications

References 47 publications

Oxidative Stress, Mitochondrial Abnormalities and Proteins Deposition: Multitarget Approaches in Alzheimer's Disease

Oxidative Stress, Mitochondrial Abnormalities and Proteins Deposition: Multitarget Approaches in Alzheimer's Disease

Monoterpenes modulating cytokines - A review

Dementia, Preclinical Studies in Neurodegeneration and its Potential for Translational Medicine in South America

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