ABSTRACT
Many physiological activities including endocrine, metabolism and immunity are regulated by circadian rhythm. Abnormal circadian rhythms are associated with a variety of diseases, including tumer, obesity, diabetes and mood disorders, as well as neurodegenerative diseases. Parkinson's disease is the second most common neurodegenerative disease, second only to Alzheimer's disease. The cardinal features of Parkinson's disease include rest tremor, bradykinesia, rigidity, and gait impairment, which are also accompanied by many non-motor symptoms. Circadian dysfunction is one of the most common non-motor symptoms of Parkinson's disease, which may occur before the onset of motor symptoms or last throughout the course of the disease, causing significant negative effects on the quality of life of patients and caregivers. In this article we review the clinical manifestations, biological markers and current treatment strategies of circadian dysfunction in Parkinson's disease.
ABSTRACT
Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1 mmol⋅L(-1)) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2 mmol⋅L(-1) CGA decreased the peak current density of IK,A. Both 0.2 mmol⋅L(-1) and 1 mmol⋅L(-1) CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects.