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Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease

Translational Neurodegeneration 2013年第1期2卷 124-133页

作者： kay cheong teo Shu-Leong Ho Division of Neurology Department of MedicineUniversity of Hong KongHong KongChina Research Centre of Heart BrainHormone and Healthy Aging(HBHA)University of Hong KongHong KongChina

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B(MAOB)inhibitors.They have been studied for their potential disease-modifying effects in Parkinson’s disease(PD)for over 20 years in various clinical trials.This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD.Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug.Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles,some of which may be insurmountable.

关键词： Parkinson's disease Monoamine oxidase-B inhibitors Disease-modification Neuroprotection Selegiline Rasagiline

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The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies:a review

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Translational Neurodegeneration 2017年第1期6卷 245-255页

作者： Shirley Yin-Yu Pang kay-cheong teo Jacob Shujui Hsu Richard Shek-Kwan Chang Miaoxin Li Pak-Chung Sham Shu-Leong Ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongPeople’s Republic of China Centre for Genomic Sciences University of Hong KongHong KongPeople’s Republic of China Department of Medical Genetics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouPeople’s Republic of China Key Laboratory of Tropical Disease Control(SYSU) Ministry of EducationGuangzhouPeople’s Republic of China

The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping symptoms.It does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same disorder.The advent of next generation sequencing(NGS)has allowed for a system-wide,unbiased approach to identify all gene variants in the genome simultaneously.With the plethora of new genes being identified,genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia(SCA),hereditary spastic paraplegia(HSP)and Charcot-Marie-Tooth disease(CMT)has become widely accepted.It has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson’s disease(PD)and amyotrophic lateral sclerosis(ALS).The observation of pleiotropy has emerged,with mutations in the same gene giving rise to diverse phenotypes,which further increases the complexity of phenotype-genotype correlation.Possible mechanisms of pleiotropy include different downstream effects of different mutations in the same gene,presence of modifier genes,and oligogenic inheritance.Future directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms,translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies,and ultimately finding disease-modifying therapies for neurodegenerative disorders.

关键词： Next generation sequencing Neurodegenerative diseases Genetics Pleiotropy

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