Parkinson Disease: Ding Y

Mines M, Ding Y, Fan GH. · Department of Veterans Affairs and the Department of Biomedical Sciences, Division of Neurobiology and Neurotoxicology, Meharry Medical College, Nashville, TN 37208, USA. · Curr Med Chem. · Pubmed #17979699 No free full text.

Abstract: Chemokines and chemokine receptors, primarily found to play a role in leukocyte migration to the inflammatory sites or to second lymphoid organs, have recently been found expressed on the resident cells of the central nervous system (CNS). These proteins are important for the development of the CNS and are involved in normal brain functions such as synaptic transmission. Increasing lines of evidence have implicated an involvement for chemokines and their receptors in several neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), human immunodeficiency virus-associated dementia (HAD), multiple sclerosis (MS), and stroke. Specific inhibition of the biological activities of chemokine receptors could gain therapeutic benefit for these neurodegenerative disorders. In recent years, non-peptide antagonists of chemokine receptors have been disclosed and tested in relevant pharmacological models and some of these inhibitors have entered clinical trials. The aim of this review is to outline the recent progress regarding the role of chemokines and their receptors in neurodegenerative diseases and the advancements in the development of chemokine receptor inhibitors as potential therapeutic approaches for these neurodegenerative diseases.

Chen L, Cagniard B, Mathews T, Jones S, Koh HC, Ding Y, Carvey PM, Ling Z, Kang UJ, Zhuang X. · Department of Neurobiology, Pharmacology and Physiology, The University of Chicago, Chicago, Illinois 60637, USA. · J Biol Chem. · Pubmed #15799973 links to  free full text

Abstract: Mutations in the DJ-1 gene were recently identified in an autosomal recessive form of early-onset familial Parkinson disease. Structural biology, biochemistry, and cell biology studies have suggested potential functions of DJ-1 in oxidative stress, protein folding, and degradation pathways. However, animal models are needed to determine whether and how loss of DJ-1 function leads to Parkinson disease. We have generated DJ-1 null mice with a mutation that resembles the large deletion mutation reported in patients. Our behavioral analyses indicated that DJ-1 deficiency led to age-dependent and task-dependent motoric behavioral deficits that are detectable by 5 months of age. Unbiased stereological studies did not find obvious dopamine neuron loss in 6-month- and 11-month-old mice. Neurochemical examination revealed significant changes in striatal dopaminergic function consisting of increased dopamine reuptake rates and elevated tissue dopamine content. These data represent the in vivo evidence that loss of DJ-1 function alters nigrostriatal dopaminergic function and produces motor deficits.

Li Y, Cai L, Shao M, Ding Y. · Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Capital University of Medical Sciences, Beijing 100053, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #11832073 No free full text.

Abstract: OBJECTIVE: To evaluate the clinical necessity, outcomes, safety, and indications of contemporary combined pallidotomy and thalamotomy for Parkinson's disease (PD) with intractable tremor. METHODS: The UPDRS data from 20 patients who received simultaneous pallidotomy and thalamotomy were analyzed retrospectively. During the same period, 326 patients were subjected to unilateral pallidotomy. Improvement and complications between the two groups were compared. RESULTS: Contemporary pallidotomy and thalamotomy effectively improved parkinsonian symptoms as did pallidotomy alone. This procedure completely abolished intractable tremor in all 20 patients. No permanent complications occurred. CONCLUSIONS: Contemporary combination of pallidotomy and thalamotomy is effective and safe in treating regular parkinsonian symptoms and intractable tremor.

Li Y, Shi C, Shao M, Ding Y. · Beijing Institute of Functional Neurosurgery, Xuanwu Hospital, Beijing 100053, China. · Zhonghua Wai Ke Za Zhi. · Pubmed #11832017 No free full text.

Abstract: OBJECTIVE: To clarify the benefits and risks of patients undergoing bilateral posteroventral pallidotomy (BPVP) for patients with idiopathic Parkinson's disease (PD) and the differences between contemporaneous BPVP (CBPVP) and staged BPVP (SBPVP). METHODS: Twenty patients underwent microelectrode-guided CBPVP and 26 SBPVP for bilateral PD symptoms. The data were retrospectively reviewed. Unified Parkinson's Disease Rating Scale (UPDRS) was used to evaluate the effects of these operations. RESULTS: BPVP, either CBPVP or SBPVP, significantly improved patients' bilateral PD symptoms (P < 0.001). The improvement was consistently higher in "off" state than in "on" state. No statistical difference was observed in the improvement percentages of CBPVP, SBPVP1 and SBPVP2. CBPVP contributed greatly to L-dopa induced side effects (part IV). BPVP, SBPVP1, and SBPVP2 significantly improved cardinal parkinsonian signs but no difference was found among them. One patient after CBPVP developed hypophonia and swallowing problem, while 2 patients after SBPVP sustained hypophonia. These conditions were improved 3 months later. CONCLUSIONS: BPVP may significantly improve bilateral signs of PD. It is safer than bilateral thalamotomy. CBPVP is applicable to some patients. BPVP may not cause mental impairment but shows a higher incidence rate of hypophonia. The practice of BPVP requires a refined surgical technique and a better understanding of pathophysiology of the basal ganglia.

Zhao G, Li Y, Shao M, Ding Y. · Beijing Institute of Functional Neurosurgery, Beijing Xuanwu Hospital, Beijing 100053. · Zhonghua Wai Ke Za Zhi. · Pubmed #11829894 No free full text.

Abstract: OBJECTIVE: To evaluate the outcome of microelectrode-guided posteroventral pallidotomy (PVP) for L-dopa induced dyskinesia in patients with Parkinson's disease. METHODS: Thirty-six patients with dyskinesia were evaluated with unified Parkinson's disease rating scale (UPDRS) before and after operation. Duration and disability of dyskinesia were analyzed respectively. RESULTS: The total surgical improvement for dyskinesia was 76.2%. Duration improvement was 88.8% and disability 79.7%. Significant change (P < 0.05) happened postoperatively. Seventeen patients were followed up for 3 months. The result showed a stable improvement for dyskinesia. CONCLUSIONS: L-dopa induced dyskinesia may disappear or be improved after PVP. Surgical treatment promises a maximum L-dopa therapy without any severe pharmaceutical complications. Synergic treatment of drug and surgery are a new strategy for Parkinson's disease.