The aetiology of idiopathic Parkinson's disease

Agents potentially involved in the aetiology of idiopathic Parkinson's disease are discussed. These include factors regulating dopaminergic neurogenesis (Nurr 1, Ptx-3, and Lmx1b) and related proteins, together with genes involved in familial Parkinson's disease (α synuclein, parkin, and ubiquitin carboxy terminal hydroxylase L1), and endogenous and environmental agents.published_or_final_versio

Central Nervous System Inflammatory Demyelinating Disorders in the Hong Kong Chinese

Central nervous system inflammatory demyelinating disorders (CNS IDD) include classical multiple sclerosis, neuromyelitis optica (NMO) spectrum disorders, a single attack of/recurrent acute disseminated encephalomyelitis, a single attack of idiopathic acute transverse myelitis, optic neuritis (ON) and brainstem encephalitis. CNS IDD are potentially serious disorders with risks of mortality and significant disability. Typical relapsing forms of CNS IDD are relapsing remitting multiple sclerosis and relapsing NMO. Relapsing NMO is typified by recurrent longitudinally extensive transverse myelitis and severe unilateral or bilateral ON. Early diagnosis of CNS IDD is important as long-term treatment for different forms varies. Recognition of clinical, radiological and serological characteristics of different forms of CNS IDD facilitates early diagnoses. A significant proportion of NMO patients are seropositive for autoantibodies against aquaporin-4, the most abundant water channel in the CNS; this supports the hypothesis that NMO is an autoimmune disorder. Is NMO an autoantibody-mediated disorder sharing similar pathogenesis with myasthenia gravis (MG), a classical autoantibody-mediated autoimmune disease? An interesting observation is that paraneoplastic NMO associated various tumours is recognised recently, suggesting similarity with MG which is associated with thymoma in about 15 to 20% of patients.published_or_final_versio

Role of mitochondrial uncoupling protein-4 in energy supply during neuronal differentiation

OBJECTIVES: Neuronal differentiation is involved in brain development. Stimulation of all-trans-retinoic acid (RA) in neuroblastoma cells results in growth inhibition, increased neuron-specific enolase (NSE) activity, and promoted axonal growth. Mitochondrial uncoupling protein-4 (UCP4) is ...published_or_final_versionThe 16th Medical Research Conference (MRC), Department of Medicine, the University of Hong Kong, Hong Kong, 22 January 2011. In Hong Kong Medical Journal, 2011, v. 17 suppl. 1, p. 31, abstract no. 4

Assessment of Cellular Estrogenic Activity Based on Estrogen Receptor-Mediated Reduction of Soluble-Form Catechol-O-Methyltransferase (COMT) Expression in an ELISA-Based System

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Mitochondrial neuronal uncoupling proteins: a target for potential disease-modification in Parkinson's disease

This review gives a brief insight into the role of mitochondrial dysfunction and oxidative stress in the converging pathogenic processes involved in Parkinson's disease (PD). Mitochondria provide cellular energy in the form of ATP via oxidative phosphorylation, but as an integral part of this process, superoxides and other reactive oxygen species are also produced. Excessive free radical production contributes to oxidative stress. Cells have evolved to handle such stress via various endogenous anti-oxidant proteins. One such family of proteins is the mitochondrial uncoupling proteins (UCPs), which are anion carriers located in the mitochondrial inner membrane. There are five known homologues (UCP1 to 5), of which UCP4 and 5 are predominantly expressed in neural cells. In a series of previous publications, we have shown how these neuronal UCPs respond to 1-methyl-4-phenylpyridinium (MPP+; toxic metabolite of MPTP) and dopamine-induced toxicity to alleviate neuronal cell death by preserving ATP levels and mitochondrial membrane potential, and reducing oxidative stress. We also showed how their expression can be influenced by nuclear factor kappa-B (NF-kappaB) signaling pathway specifically in UCP4. Furthermore, we previously reported an interesting link between PD and metabolic processes through the protective effects of leptin (hormone produced by adipocytes) acting via UCP2 against MPP+-induced toxicity. There is increasing evidence that these endogenous neuronal UCPs can play a vital role to protect neurons against various pathogenic stresses including those associated with PD. Their expression, which can be induced, may well be a potential therapeutic target for various drugs to alleviate the harmful effects of pathogenic processes in PD and hence modify the progression of this disease.published_or_final_versio

The effect of ex-vivo rotenone intoxication on dopamine re-uptake of LRRK2-R1441G mutant mouse

Poster presentationpublished_or_final_versio

Combined LRRK2 mutation, aging and chronic low dose oral rotenone as a model of Parkinson’s disease

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LRRK2 R1441G mice are more liable to dopamine depletion and locomotor inactivity

postprin

Cross-sectional evaluation of a longitudinal consultation skills course at a new UK medical school

Background: Good communication is a crucial element of good clinical care, and it is important to provide appropriate consultation skills teaching in undergraduate medical training to ensure that doctors have the necessary skills to communicate effectively with patients and other key stakeholders. This article aims to provide research evidence of the acceptability of a longitudinal consultation skills strand in an undergraduate medical course, as assessed by a cross-sectional evaluation of students' perceptions of their teaching and learning experiences. Methods: A structured questionnaire was used to collect student views. The questionnaire comprised two parts: 16 closed questions to evaluate content and process of teaching and 5 open-ended questions. Questionnaires were completed at the end of each consultation skills session across all year groups during the 2006-7 academic year (5 sessions in Year 1, 3 in Year 2, 3 in Year 3, 10 in Year 4 and 10 in Year 5). 2519 questionnaires were returned in total. Results: Students rated Tutor Facilitation most favourably, followed by Teaching, then Practice & Feedback, with suitability of the Rooms being most poorly rated. All years listed the following as important aspects they had learnt during the session: • how to structure the consultation • importance of patient-centredness • aspects of professionalism (including recognising own limits, being prepared, generally acting professionally). All years also noted that the sessions had increased their confidence, particularly through practice. Conclusions: Our results suggest that a longitudinal and integrated approach to teaching consultation skills using a well structured model such as Calgary-Cambridge, facilitates and consolidates learning of desired process skills, increases student confidence, encourages integration of process and content, and reinforces appreciation of patient-centredness and professionalism

Gene mapping of familial amyotrophic lateral sclerosis

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disorder characterized by gradual death of motor neurons in cerebral cortex, brain stem, and spinal cord. The pathogenetic mechanism remains unclear for the vast majority of cases. About 10% of ALS cases are familial (FALS). Cu/Zn superoxide dismutase (SOD1) gene accounts for about 10% of autosomal dominant FALS and the gene(s) responsible for the rest of ALS/ FALS remain(s) to be found. METHOD: We recruited a large Chinese kindred without SOD1 mutation for linkage analysis. Peripheral blood samples were collected and DNA were extracted from peripheral lymphocyte. We screened the family with ~ 400 polymorphic microsatellite markers. The genotyping data were subjected to model-based and model-free linkage analysis. RESULT: Using MLINK of LINKAGE (Ver 5.2) package, we found a maximum LOD score of 4.357, ?[m=f]=0.0 at a microsatellite marker located at distal long arm of chromosome 8. Multipoint analysis by GENEHUNTER (Ver 1.2) revealed a maximum multipoint LOD score of 3.909 and NPL score 9.209. Haplotype analyses revealed a critical region which spanned 10.18-cM on chromosome 8. CONCLUSION: We identified a 10.18-cM critical FALS region on chromosome 8. Further analyses using positional cloning and candidate gene approach are indicated to delineate the underlying genetic defect for FALS in this family.published_or_final_versio