Epidemiology of Parkinson's disease

Lau, Lonneke M. L. de; Breteler, Monique M.B.

doi:10.1016/s1474-4422(06)70471-9

Cited by 3,538 publications

(2,033 citation statements)

References 106 publications

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“…Genes identified as directly associated with PD include SNCA, PRKN, PINK1, DJ-1, and LRRK2. There are diverging estimates of the contribution of mutations in these genes to PD, with estimates ranging from less than 5 % (Pankratz and Foroud 2007) to about 10 % of all cases of PD (de Lau and Breteler 2006). However, the frequency of some forms of primary genetic parkinsonism is very population dependent; for example LRRK2 parkinsonism accounts for approximately 40 % of familial PD in Tunisians and <3 % in North Americans (Ishihara et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease

Scuffham

McInerny-Leo

et al. 2013

J Community Genet

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Advances in genetic tests provide valuable information for clinicians and patients around risks and inheritance of Parkinson's Disease (PD); however, questions arise whether those affected or at risk of PD will want genetic testing, particularly given that there are no preventive or diseasemodifying therapies currently available. This study sought to determine knowledge and attitudes toward genetic testing for those affected with PD. A cross-sectional study was undertaken using a standardized questionnaire with six multi-choice genetic knowledge and 17 multi-choice attitude items. Participants were selected from a registry of people affected with PD living in Queensland, Australia. Half of the selected index cases had a family history of PD. Ordinal regression was used to evaluate the association between support for genetic testing and demographic, knowledge, and other attitudinal factors. The level of genetic knowledge was relatively low (37 % correct responses). The vast majority supported diagnostic testing (97 %) and 90 % would undertake a genetic test themselves. Support for predictive was lower (78 %) and prenatal genetic testing had the least support (58 %). Benefits of testing were identified as the ability to know the child's risk, seek therapies, and helping science with finding a cure. Concerns about genetic testing included potential emotional reactions and test accuracy. Genetic knowledge was not significantly associated with attitudes towards genetic testing. Patients with PD have strong interest in genetic testing for themselves with support for diagnostic testing but less support for predictive and prenatal testing. Genetic knowledge was unrelated to testing attitudes.

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Section: Introductionmentioning

confidence: 99%

Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease

Scuffham

McInerny-Leo

et al. 2013

J Community Genet

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“…PD is the second most common degenerative disease, characterized by the specifi c loss of dopaminergic neurons in the substantia nigra pars compacta [53] . Although the etiologies of PD remain elusive, protein dyshomeostasis is the critical mechanism responsible for the neuronal death and may be involved in the pathogenesis.…”

Section: Parkinson's Disease (Pd)mentioning

confidence: 99%

Chaperone-mediated autophagy: roles in neuroprotection

et al. 2015

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Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal proteolysis, is characterized by the selective targeting and direct translocation into the lysosomal lumen of substrate proteins containing a targeting motif biochemically related to the pentapeptide KFERQ. Along with the other two lysosomal pathways, macro-and micro-autophagy, CMA is essential for maintaining cellular homeostasis and survival by selectively degrading misfolded, oxidized, or damaged cytosolic proteins. CMA plays an important role in pathologies such as cancer, kidney disorders, and neurodegenerative diseases. Neurons are post-mitotic and highly susceptible to dysfunction of cellular quality-control systems. Maintaining a balance between protein synthesis and degradation is critical for neuronal functions and homeostasis. Recent studies have revealed several new mechanisms by which CMA protects neurons through regulating factors critical for their viability and homeostasis. In the current review, we summarize recent advances in the understanding of the regulation and physiology of CMA with a specifi c focus on its possible roles in neuroprotection.Keywords: chaperone-mediated autophagy; cellular homeostasis; neuroprotection; neuronal death; neurodegenerative disease ·Review· IntroductionMaintaining the balance between protein synthesis and degradation contributes to cellular homeostasis [1][2][3] . The ubiquitin-proteasome system (UPS) and the autophagylysosome pathway (ALP) are major systems present in almost all cell types to mediate the degradation of intracellular proteins into their constitutive amino-acids [4,5] .The UPS is a multi-subunit protease complex that degrades proteins tagged with one or more covalently-bound ubiquitin molecules, and most proteasome substrates are proteins with a short half-life [6,7] .In contrast to the UPS, the ALP is mainly responsible for the degradation of long-lived proteins and organelles.On the basis of the mechanism used for delivery of intracellular cargoes to lysosomes, autophagy can be divided into three types: macroautophagy (MA), microautophagy, and chaperone-mediated autophagy (CMA) [8,9] . Both CMA and MA have been identified in mammals as processes important for damage and diseases of the central nervous system [10] . MA is a bulk degradation system that involves the formation of a double-membrane structure (autophagosome) that sequesters damaged organelles and proteins. The autophagosome acquires the hydrolytic enzymes necessary to degrade its cargo by fusing with lysosomes [11] . Microautophagy traps nonspecifi c cytoplasm inside vesicles via direct invagination of the lysosomal membrane. These vesicles "pinch off" into the lumen and are degraded by lysosomal hydrolases [12] .CMA is the third type of autophagy, and has so far been found only in mammalian cells [13,14] . One of its intrinsic features is the selective targeting and direct translocation into the lysosomal lumen of substrate proteins containing a targeting motif related to the pentapeptide KFERQ [15,16] [17][1...

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“…PD is the second most common chronic neurodegenerative disease, after Alzheimer's disease, affecting nearly 1% of the population over the age of 65 1. The prevalence of PD is expected to double in the next 20 years in the world's most populous nations 2.…”

Section: Introductionmentioning

confidence: 99%

A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY‐PD III)

Biglan

Oakes

Lang

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo describe the rationale for a novel study design and baseline characteristics of a disease‐modifying trial of isradipine 10 mg daily in early Parkinson disease (PD).Methods STEADY‐PDIII is a 36‐month, Phase 3, parallel group, placebo‐controlled study of the efficacy of isradipine 10 mg daily in 336 participants with early PD as measured by the change in the Unified Parkinson Disease Rating Scale (UPDRS) Part I‐III score in the practically defined ON state. Secondary outcome measures include clinically meaningful measures of disability progression in early PD: (1) Time to initiation and utilization of dopaminergic therapy; (2) Time to onset of motor complications; (3) Change in nonmotor disability. Exploratory measures include global measures of functional disability, quality of life, change in the ambulatory capacity, cognitive function, and pharmacokinetic analysis. Rationale for the current design and alternative design approaches are discussed.ResultsThe entire cohort of 336 participants was enrolled at 55 Parkinson Study Group sites in North America. The percentage of male participants were 68.5% with a mean age of 61.9 years (sd 9.0), mean Hoehn and Yahr stage of 1.7 (sd 0.5), mean UPDRS total of 23.1 (sd 8.6), and MoCA of 28.1 (sd 1.4).Interpretation STEADY‐PD III has a novel and innovative design allowing for the determination of longer duration benefits on clinically relevant outcomes in a relatively small cohort on top of the benefit derived from symptomatic therapy. Baseline characteristics are similar to those in previously enrolled de novo PD trials. This study represents a unique opportunity to evaluate the potential impact of a novel therapy to slow progression of PD disability and provide clinically meaningful benefits.

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Epidemiology of Parkinson's disease

Cited by 3,538 publications

References 106 publications

Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease

Knowledge and attitudes towards genetic testing in those affected with Parkinson’s disease

Chaperone-mediated autophagy: roles in neuroprotection

A novel design of a Phase III trial of isradipine in early Parkinson disease (STEADY‐PD III)

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