Abstract
The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson's disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.
Highlights
The imbalance between reactive oxygen species (ROS) generation and cellular antioxidant activity leading to oxidative stress is known to be a major cause of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]
The results showed that ROS levels in eye imaginal discs were 2.3-fold higher in knockdown larvae carrying GMR-GAL4/Y; +; UAS-dUCH.IR/+ than in control larvae carrying GMR-GAL4/Y; +; + (Figures 1(a), 1(b), and 1(d))
These results suggest that the knockdown of dUCH increased ROS levels in Drosophila
Summary
The imbalance between reactive oxygen species (ROS) generation and cellular antioxidant activity leading to oxidative stress is known to be a major cause of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) [1]. Antioxidants are regarded as a potential treatment for neurodegenerative disorders including PD [2, 3]. PD affects 1% of the population aged older than 60 years and is considered to be the second most common neurodegenerative disorder after AD. PD is characterized by progressive impairments in locomotive ability such as tremor, rigidity, and bradykinesia. These symptoms are attributed to the loss of dopaminergic neurons (DA neurons) in the substantia
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