Deep brain stimulation (DBS) has become an effective therapeutic option for neurological and psychiatric disorders such as Parkinson’s disease (PD), dystonia, and obsessive-compulsive disorder. The subthalamic nucleus (STN) and internal globus pallidus (GPi) are by far the most commonly used targets for DBS in the treatment of PD. However, STN/GPi stimulation sometimes causes side effects, including motor fluctuations, cognitive declines, and worse emotional experience, which affect patients’ postoperative quality of life. Recent invasive electrophysiological studies are driven by the desire to better understand the mechanisms of therapeutic actions and side effects of STN/GPi stimulation. These studies investigated the function of the STN and GPi in motor, cognitive and affective processes by recording single-neuron firing patterns during the surgery or local field potentials after the surgery. Here we review the relevant studies to provide an integrative picture of the functional roles of the STN and GPi within the basal ganglia loops for motor, cognition, and emotion. Previous studies suggested that STN and GPi gamma oscillations encode the strength and speed of voluntary movements (execution), whereas beta oscillations reflect the effort and demand of potential movements (preparation). In the cognitive domain, oscillatory beta activity in the STN is involved when people have to stop an inappropriate action or to suppress salient but task-irrelevant information, whereas theta/delta activity is associated with the adjustment of decision thresholds and cost-benefit trade-off. In the affective domain, STN activity in the alpha band may represent the valence and arousal of emotional information.

The JAK (Janus kinase) family members play a role in the transmission of signals from extracellular stimuli across the plasma membrane via the cytoplasm to the nucleus in eukaryotes. The JAK family is comprised of JAK1, JAK2, JAK3 and TYK2 (tyrosine kinase 2), and the complexities underlying their activation and regulation are still being investigated. Here, we review the recent advances of their functions and the underlying mechanism of activation. At the molecular level, recent studies have greatly advanced our knowledge of the structures and organization of the JAK proteins, as well as the mechanism of JAK activation, particularly the role of the pseudokinase domain as a suppressor of the adjacent tyrosine kinase domain’s catalytic activity. We also review recent advances in our understanding of the mechanisms of negative regulation exerted by phosphatase and SH2 (Src homology 2) domain-containing proteins. These recent studies highlight the diversity of regulatory mechanisms utilized by the JAK family to maintain signalling fidelity, and shed much light on the potential novel strategies for precise treatment of the associated diseases.

In Parkinson’s disease (PD), the alpha-synuclein (α-syn) pathology occurs both in the enteric nervous system (ENS) and parasympathetic nerves in the early stage of PD, which precedes the central nervous system (CNS) pathology and is related to gastrointestinal dysfunction precedes the onset of motor symptoms in PD. Studies have shown that gut microbiota can affect brain activity through the microbiota-gut-brain axis in PD patients. They can promote the development of PD and might be the origin of PD. There are four communication routes between gut microbiota and brain, which respectively are the gut-brain’s neural network, endocrine system, gut immune system, and barrier paths which include intestinal mucosal barrier and blood-brain barrier (BBB). Based on the alteration of fecal microbiota composition in PD, it is worthwhile to investigate whether microbiota analysis could be used as a biomarker for premotor PD. As a potential therapy, fecal microbiota transplantation (FMT) may be a promising treatment for PD patients. Further studies are needed to elucidate the causal relationship between gut microbiota and PD.

Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.