Curcumin exposure induces expression of the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) in rat mesencephalic cells

Ortíz-Ortíz, Miguel A.; Morán, José M.; Ruiz-Mesa, Luz M.; Niso-Santano, Mireia; Bravo-SanPedro, José M.; Gómez-Sánchez, Rubén; González‐Polo, Rosa A.; Fuentes, José

doi:10.1016/j.neulet.2009.10.081

Cited by 29 publications

(19 citation statements)

References 47 publications

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“…Furthermore, adding curcumin to flies’ diet protects them against H 2 O 2 and increases their survival [401]. A proposed mechanism for this protective effect is increased expression of LRRK2 [402]. Despite the limitations of over-expression paradigms, one can conclude from these results that LRRK2 has an important role in mitochondrial function and in the capacity of the cell to keep oxidative stress in check.…”

Section: The Role Of Pd-related Proteins In Oxidative Stressmentioning

confidence: 99%

The Role of Oxidative Stress in Parkinson's Disease

Dias

Junn

Mouradian

2013

Journal of Parkinson's Disease

1,399

978

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Oxidative stress plays an important role in the degeneration of dopaminergic neurons in Parkinson’s disease (PD). Disruptions in the physiologic maintenance of the redox potential in neurons interfere with several biological processes, ultimately leading to cell death. Evidence has been developed for oxidative and nitrative damage to key cellular components in the PD substantia nigra. A number of sources and mechanisms for the generation of reactive oxygen species (ROS) are recognized including the metabolism of dopamine itself, mitochondrial dysfunction, iron, neuroinflammatory cells, calcium, and aging. PD causing gene products including DJ-1, PINK1, parkin, alpha-synuclein and LRRK2 also impact in complex ways mitochondrial function leading to exacerbation of ROS generation and susceptibility to oxidative stress. Additionally, cellular homeostatic processes including the ubiquitin-proteasome system and mitophagy are impacted by oxidative stress. It is apparent that the interplay between these various mechanisms contributes to neurodegeneration in PD as a feed forward scenario where primary insults lead to oxidative stress, which damages key cellular pathogenetic proteins that in turn cause more ROS production. Animal models of PD have yielded some insights into the molecular pathways of neuronal degeneration and highlighted previously unknown mechanisms by which oxidative stress contributes to PD. However, therapeutic attempts to target the general state of oxidative stress in clinical trials have failed to demonstrate an impact on disease progression. Recent knowledge gained about the specific mechanisms related to PD gene products that modulate ROS production and the response of neurons to stress may provide targeted new approaches towards neuroprotection.

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Section: The Role Of Pd-related Proteins In Oxidative Stressmentioning

confidence: 99%

The Role of Oxidative Stress in Parkinson's Disease

Dias

Junn

Mouradian

2013

Journal of Parkinson's Disease

1,399

978

View full text Add to dashboard Cite

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“…Moreover, in PD animal models, exposure of rat mesencephalic cells to curcumin induces the expression of LRRK2 at the mRNA and protein level; LRRK2 overexpression is strongly associated with pathological cellular inclusions found in several neurodegenerative disorders (472). Curcumin has also been identified as an activator of apoptosis.…”

Section: E Free Radical Scavengersmentioning

confidence: 99%

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Bernhardi

Eugenı́n

2012

Antioxidants & Redox Signaling

161

113

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Alzheimer's disease (AD) is the most common cause of dementia and a progressive neurodegeneration that appears to result from multiple pathogenic mechanisms (including protein misfolding/aggregation, involved in both amyloid β-dependent senile plaques and tau-dependent neurofibrillary tangles), metabolic and mitochondrial dysfunction, excitoxicity, calcium handling impairment, glial cell dysfunction, neuroinflammation, and oxidative stress. Oxidative stress, which could be secondary to several of the other pathophysiological mechanisms, appears to be a major determinant of the pathogenesis and progression of AD. The identification of oxidized proteins common for mild cognitive impairment and AD suggests that key oxidation pathways are triggered early and are involved in the initial progression of the neurodegenerative process. Abundant data support that oxidative stress, also considered as a main factor for aging, the major risk factor for AD, can be a common key element capable of articulating the divergent nature of the proposed pathogenic factors. Pathogenic mechanisms influence each other at different levels. Evidence suggests that it will be difficult to define a single-target therapy resulting in the arrest of progression or the improvement of AD deterioration. Since oxidative stress is present from early stages of disease, it appears as one of the main targets to be included in a clinical trial. Exploring the articulation of AD pathogenic mechanisms by oxidative stress will provide clues for better understanding the pathogenesis and progression of this dementing disorder and for the development of effective therapies to treat this disease.

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“…Although most studies support the role of curcumin against PD, a few have found that curcumin worsens the disease. For example, exposure of rat mesencephalic cells to curcumin induced the expression of LRRK2 mRNA and protein in a time-dependent manner [67]. As LRRK2 overexpression is strongly associated with the pathological inclusions found in several neurodegenerative disorders, the latter authors concluded that the role of curcumin as a therapeutic agent for PD needs thorough investigation.…”

Section: Neuroprotection By Nutraceuticalsmentioning

confidence: 99%

Neuroprotection by Spice-Derived Nutraceuticals: You Are What You Eat!

et al. 2011

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Numerous lines of evidence indicate that chronic inflammation plays a major role in the development of various neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, brain tumor, and meningitis. Why these diseases are more common among people from some countries than others is not fully understood, but lifestyle factors have been linked to the development of neurodegenerative diseases. For example, the incidence of certain neurodegenerative diseases among people living in the Asian subcontinent, where people regularly consume spices, is much lower than in countries of the western world. Extensive research over the last 10 years has indicated that nutraceuticals derived from such spices as turmeric, red pepper, black pepper, licorice, clove, ginger, garlic, coriander, and cinnamon target inflammatory pathways, thereby may prevent neurodegenerative diseases. How these nutraceuticals modulate various pathways and how they exert neuroprotection are the focus of this review.

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Curcumin exposure induces expression of the Parkinson's disease-associated leucine-rich repeat kinase 2 (LRRK2) in rat mesencephalic cells

Cited by 29 publications

References 47 publications

The Role of Oxidative Stress in Parkinson's Disease

The Role of Oxidative Stress in Parkinson's Disease

Alzheimer's Disease: Redox Dysregulation As a Common Denominator for Diverse Pathogenic Mechanisms

Neuroprotection by Spice-Derived Nutraceuticals: You Are What You Eat!

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