Advances in the genetics of Parkinson disease

Trinh, Joanne; Farrer, Matthew J.

doi:10.1038/nrneurol.2013.132

Cited by 424 publications

(317 citation statements)

References 168 publications

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“…R. Soc. B 370: 20140185 exocytosis, endocytosis and vesicle recycling, each of which has also been implicated causally in degeneration in PD and PD mouse models [158][159][160]. Strikingly, however, most evidence for release dysfunction in PD models has come from studies of glutamate release, plus a few studies of axonal DA releasebut no studies of somatodendritic DA release-amplifying the value of mechanistic studies of this release process.…”

Section: Conclusion and Open Questionsmentioning

confidence: 99%

Somatodendritic dopamine release: recent mechanistic insights

Rice

Patel

2015

Phil. Trans. R. Soc. B

101

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One contribution of 16 to a discussion meeting issue 'Release of chemical transmitters from cell bodies and dendrites of nerve cells'. Dopamine (DA) is a key transmitter in motor, reward and cogitative pathways, with DA dysfunction implicated in disorders including Parkinson's disease and addiction. Located in midbrain, DA neurons of the substantia nigra pars compacta project via the medial forebrain bundle to the dorsal striatum (caudate putamen), and DA neurons in the adjacent ventral tegmental area project to the ventral striatum (nucleus accumbens) and prefrontal cortex. In addition to classical vesicular release from axons, midbrain DA neurons exhibit DA release from their cell bodies and dendrites. Somatodendritic DA release leads to activation of D2 DA autoreceptors on DA neurons that inhibit their firing via G-protein-coupled inwardly rectifying K þ channels. This helps determine patterns of DA signalling at distant axonal release sites. Somatodendritically released DA also acts via volume transmission to extrasynaptic receptors that modulate local transmitter release and neuronal activity in the midbrain. Thus, somatodendritic release is a pivotal intrinsic feature of DA neurons that must be well defined in order to fully understand the physiology and pathophysiology of DA pathways. Here, we review recent mechanistic aspects of somatodendritic DA release, with particular emphasis on the Ca 2þ dependence of release and the potential role of exocytotic proteins.

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Section: Conclusion and Open Questionsmentioning

confidence: 99%

Somatodendritic dopamine release: recent mechanistic insights

Rice

Patel

2015

Phil. Trans. R. Soc. B

101

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“…It can also be accompanied by various non-motor symptoms, including sleep, autonomic, sensory, cognitive, and psychiatric disturbances. Nearly all forms of Parkinson's disease result from reduced dopaminergic transmission in the basal ganglia [50,51]. Many genes, mutations, and polymorphisms have been implicated in the pathogenesis of the disease.…”

Section: Parkinson's Diseasementioning

confidence: 99%

Autophagy and human diseases

2013

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Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized.

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“…It has an age‐dependent prevalence, and its burden at the population level is estimated to expand dramatically as the size of elderly population grows (Dorsey et al., 2007; Trinh & Farrer, 2013). The majority of patients with PD are sporadic forms, probably resulting from the interactions between genetic and environmental factors (Migliore & Coppede, 2009).…”

Section: Introductionmentioning

confidence: 99%

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese

Wang

Sun

et al. 2018

Brain and Behavior

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ObjectivesStudies at the genomewide level of Parkinson's disease (PD) suggested a significant association between the Hydroxy‐delta‐5‐steroid dehydrogenase, 3 beta‐ and steroid delta isomerase 7 (HSD3B7) gene rs9938550 variant and a decreased risk for PD. But its effect has only been discussed in Caucasian populations, and no phenotypic characteristics were included. To investigate the novel variant for PD in Chinese Han populations, we performed an association analysis of rs9938550 variant in a large cohort.MethodsUsing a case–control methodology, a total of 2,239 subjects (1,072 sporadic patients with PD and 1,167 control) were genotyped and the genetic association was analyzed.ResultsNo significant association was found between allele A of rs9938550 and PD in the entire cohort (p = .079). However, the frequency of allele A was lower in late‐onset PD (LOPD) as compared with controls older than 50 years (OR = 0.62, 95% CI: 0.45–0.85, p adjust = .002). Relatively lower Unified Parkinson's Disease Rating Scale scores were demonstrated in mid‐ to late‐stage PD with GA + AA genotypes than GG genotype (p adjust = .018), while other clinical features were similar between carriers and noncarriers.ConclusionsOur results support that the HSD3B7 rs9938550 variant, which is likely linked to bile acid biosynthesis, reduces the risk of LOPD in Chinese patients and might induce a benign clinical performance.

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Advances in the genetics of Parkinson disease

Cited by 424 publications

References 168 publications

Somatodendritic dopamine release: recent mechanistic insights

Somatodendritic dopamine release: recent mechanistic insights

Autophagy and human diseases

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese

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