Decreased expression of Bmal2 in patients with Parkinson's disease

Ding, Hui; Liu, Shu; Yuan, Yanpeng; Lin, Qingling; Chan, Piu; Cai, Yanning

doi:10.1016/j.neulet.2011.05.058

Cited by 58 publications

(44 citation statements)

References 18 publications

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“…Clock, Npas2 and Bmal1 are the transcriptional activators of circadian clock system, which form a heterodimer to activate the feedback control genes Per and Cry (Buhr and Takahashi 2013; Partch et al 2014). In PD patients, sleep dysfunction seen in early Parkinson’s disease may reflect a more fundamental pathology in the molecular clock underlying circadian rhythms (Breen et al 2014; Verwey et al 2016), and decreased expression of Bmal1 (Cai et al 2010) and Bmal2 (Ding et al 2011) in leukocytes of PD patients was reported. Consistent with these observations, the expression of core clock genes Bmal1 and clock was decreased in a MPTP mouse model of PD (Hayashi et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats

Song

Wang

et al. 2018

Neurotox Res

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A single injection of LPS produced low-grade neuroinflammation leading to Parkinson’s disease (PD) in mice several months later. Whether such a phenomenon occurs in rats and whether such low-grade neuroinflammation would aggravate rotenone (ROT) neurotoxicity and disrupts circadian clock gene/protein expressions were examined in this study. Male rats were given two injections of LPS (2.5–7.5 mg/kg), and neuroinflammation and dopamine neuron loss were evident 3 months later. Seven months after a single LPS (5 mg/kg) injection, rats received low doses of ROT (0.5 mg/kg, sc, 5 times/week for 4 weeks) to examine low-grade neuroinflammation on ROT toxicity. LPS plus ROT produced more pronounced non-motor and motor dysfunctions than LPS or ROT alone in behavioral tests, and decreased mitochondrial complex 1 activity, together with aggravated neuroinflammation and neuron loss. The expressions of clock core genes brain and muscle Arnt-like protein-1 (Bmal1), locomotor output cycles kaput (Clock), and neuronal PAS domain protein-2 (Npas2) were decreased in LPS, ROT and LPS plus ROT groups. The expressions of circadian feedback genes Periods (Per1 and Per2) were also decreased, but Cryptochromes (Cry1 and Cry2) were unaltered. The circadian clock target genes nuclear receptor Rev-Erbα (Nr1d1), and D-box-binding protein (Dbp) expressions were also decreased. Consistent with the transcript levels, circadian clock protein BMAL1, CLOCK, NR1D1 and DBP were also decreased. Thus, LPS-induced chronic low-grade neuroinflammation potentiated ROT neurotoxicity and disrupted circadian clock gene/protein expression, suggesting a role of disrupted circadian in PD development and progression.

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Section: Discussionmentioning

confidence: 99%

Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats

Song

Wang

et al. 2018

Neurotox Res

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“…They found decreased levels of BMAL1, but not PER1, and further described a correlation between PD severity and BMAL1 expression levels (24). Another study found that BMAL2 also had significantly lower levels of expression in patients with PD than controls, suggesting a dysregulation of molecular clock components in patients with PD (44). Thus, both of these diseases, and many neurodegenerative diseases in general, seem to have strong oxidative stress and circadian rhythm components.…”

Section: Neurodegenerative Diseasesmentioning

confidence: 97%

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

Wilking

Ndiaye²,

Mukhtar³

et al. 2013

Antioxidants & Redox Signaling

247

192

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Significance: Oxygen and circadian rhythmicity are essential in a myriad of physiological processes to maintain homeostasis, from blood pressure and sleep/wake cycles, down to cellular signaling pathways that play critical roles in health and disease. If the human body or cells experience significant stress, their ability to regulate internal systems, including redox levels and circadian rhythms, may become impaired. At cellular as well as organismal levels, impairment in redox regulation and circadian rhythms may lead to a number of adverse effects, including the manifestation of a variety of diseases such as heart diseases, neurodegenerative conditions, and cancer. Recent Advances: Researchers have come to an understanding as to the basics of the circadian rhythm mechanism, as well as the importance of the numerous species of oxidative stress components. The effects of oxidative stress and dysregulated circadian rhythms have been a subject of intense investigations since they were first discovered, and recent investigations into the molecular mechanisms linking the two have started to elucidate the bases of their connection. Critical Issues: While much is known about the mechanics and importance of oxidative stress systems and circadian rhythms, the front where they interact has had very little research focused on it. This review discusses the idea that these two systems are together intricately involved in the healthy body, as well as in disease. Future Directions: We believe that for a more efficacious management of diseases that have both circadian rhythm and oxidative stress components in their pathogenesis, targeting both systems in tandem would be far more successful.

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“…And the relative Bmal1 level had a correlation with motor severity and sleep quality [89]. In addition, this group continued to check other key circadian genes in PD, and the results showed that the expression pattern of Bmal2, but not Clock or Dec1, was altered compared to controls [90]. Recently, Cai and his coworkers also tested genetic polymorphisms in circadian disruptions and their susceptibility to PD pathogenesis.…”

Section: Clock Gene Differencementioning

confidence: 98%

A New Perspective for Parkinson’s Disease: Circadian Rhythm

Wang

et al. 2016

Neurosci. Bull.

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Circadian rhythm is manifested by the behavioral and physiological changes from day to night, which is controlled by the pacemaker and its regulator. The former is located at the suprachiasmatic nuclei (SCN) in the anterior hypothalamus, while the latter is composed of clock genes present in all tissues. Circadian desynchronization influences normal patterns of day-night rhythms such as sleep and alertness cycles, rest and activity cycles. Parkinson's disease (PD) exhibits diurnal fluctuations. Circadian dysfunction has been observed in PD patients and animal models, which may result in negative consequences to the homeostasis and even exacerbate the disease progression. Therefore, circadian therapies, including light stimulation, physical activity, dietary and social schedules, may be helpful for PD patients. However, the cellular and molecular mechanisms that underlie the circadian dysfunction in PD remain elusive. Further research on circadian patterns is needed. This article summarizes the existing research on the circadian rhythms in PD, focusing on the clinical symptom variations, molecular changes, as well as the available treatment options.

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Decreased expression of Bmal2 in patients with Parkinson's disease

Cited by 58 publications

References 18 publications

Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats

Low-Grade Inflammation Aggravates Rotenone Neurotoxicity and Disrupts Circadian Clock Gene Expression in Rats

Circadian Rhythm Connections to Oxidative Stress: Implications for Human Health

A New Perspective for Parkinson’s Disease: Circadian Rhythm

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