editorial familial parkinson s...
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EditorialFamilial Parkinson’s Disease/Parkinsonism
Hiroyuki Tomiyama,1 Suzanne Lesage,2 Eng-King Tan,3 and Beom S. Jeon4
1Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan2Sorbonne Universites, UPMC Universite Paris 6 UMRS 1127, Inserm U 1127, CNRS UMR 7225,Institut du Cerveau et de la Moelle Epiniere (ICM), Paris, France3Department of Neurology, Singapore General Hospital and Neuroscience & Behavioral Disorders Program,Duke-NUS Graduate Medical School, National Neuroscience Institute, Singapore4Department of Neurology, Seoul National University Hospital, Seoul, Republic of Korea
Correspondence should be addressed to Hiroyuki Tomiyama; [email protected]
Received 16 December 2014; Accepted 24 December 2014
Copyright © 2015 Hiroyuki Tomiyama et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.
Parkinson’s disease (PD) is the second most commonneurodegenerative disorder characterized by parkinsonism(bradykinesia, resting tremor, rigidity, and postural instabil-ity) with good response to L-dopa. Although the majority ofPD patients are sporadic, it is now clear that genetic factorscontribute to the pathogenesis of PD. Indeed, PARK 1-20 locihave been identified in typical and atypical parkinsonism.Furthermore, a new causative gene for PD was identified inJapanese families very recently. Knowledge and understand-ing of these conditions have led to the development of animalmodels, successful therapies, and novel tools to characterizethese clinical conditions and provide better care to patients.
In this special issue, we can see 8 papers (original researcharticles and review articles) as follows.
H. Park et al. reviewed the epidemiologic, clinical, genetic,and pathologic features of parkinsonism in spinocerebellarataxia (SCAs). They highlighted parkinsonism related toSCA2, SCA3, and SCA17 in Asia, especially in Korea. Theyshowed that parkinsonism in SCAs has the geographic dif-ferences in prevalence. Further insights into parkinsonism inSCAs might give us the new concept in the pathologicmechanisms.
About SNCA (alpha-synuclein, PARK1), we can see twopapers. Y. Huang et al. investigated independent and jointeffects ofMAPT and SNCA on PD onset age. In their originalarticle, they reported that the SNCA variants independentlyinfluence onset age of Parkinson’s disease in Chinese and
Australians.Then,M. A. Busquets et al. reviewed a hot buttonissue of the ability of alpha-synuclein to misfold in amyloidconformations and to spread via neuron-to-neuron transmis-sion, suggesting a prion-like behavior. They described thatthe high neuronal toxicity of both mature fibres and oligo-meric species, as well as the intracellular localization of theprotein and the difficulty to be secreted, could be key factorsimpeding the prion ability of alpha-synuclein aggregates.These two papers had important discussions on the role ofthe SNCA gene and alpha-synuclein as the key molecule inPD/parkinsonism.
V. Drouet et al. reviewed the identified gene, SYNJ1(encoding for Synaptojanin 1), mutation in PD and dis-cussed further insight into the neuropathological mecha-nisms. Recently, homozygous SYNJ1 Arg258Gln mutation inone of SYNJ1 functional domains was found in three unre-lated families with early-onset atypical parkinsonism withbradykinesia, dystonia, and variable atypical symptoms suchas cognitive decline, seizures, and eyelid apraxia. SYNJ1 wasdesignated as PARK20 most recently. Identification of SYNJ1can further support the fact that most of the known PD genescode for proteins playing a role in synaptic vesicle recyclingand lipidmetabolism, pointing out that synapticmaintenanceis a key player in PD pathological mechanisms.
X. Yang et al. reviewed current knowledge about theATP13A2 gene, clinical characteristics of patients with PD-associated ATP13A2 mutations, and models of how the
Hindawi Publishing CorporationBioMed Research InternationalVolume 2015, Article ID 736915, 2 pageshttp://dx.doi.org/10.1155/2015/736915
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ATP13A2 protein may help prevent neurodegeneration byinhibiting 𝛼-synuclein aggregation and supporting normallysosomal and mitochondrial function. They also discussedanotherATP13A2mutation that was associatedwith neuronalceroid lipofuscinoses (NCLs) and they proposed a singlepathway whereby ATP13A2 mutations may contribute toNCLs and parkinsonism.
S. Scuderi et al. discussed that alternative splicing inPARK2 generates the expression of different PARK2 (Parkin)protein isoforms and leads to selective degeneration ofdopaminergic neurons based on evidences in human, rat,andmouse brains. Finally, they described that understandingPARK2 alternative splicing could open up new scenarios forthe resolution of some parkinsonian syndrome. Also, A. Kh.Alieva et al. reported involvement of endocytosis and alter-native splicing in the formation of the pathological process inthe early stages of PD.Theydemonstrated a significant changein the levels of transcripts included in the large groups ofprocesses associated with the functioning of the immune sys-tem and cellular transport. Moreover, a significant change inthe splicing of genes involved in cellular-transport processeswas shown in their study. Alternative splicing should beconsidered as another pathway of regulation of the geneexpression which can lead to neurodegeneration.
A. A. Gopalai et al. conducted a large genetic studyand reported common LRRK2 (PARK8) G2385R and R1628Pvariants associated with an increased risk of PD in theMalaysian population. They provided new positive data onthe LRRK2 variants in Asian (Chinese, Taiwanese, Japanese,Singaporean, and Korean) populations.
In this special issue, they highlighted advances in geneticfindings of PD/parkinsonism and findings about the diseasemechanism and pathogenesis which can lead to therapeuticstrategy for PD/parkinsonism. Their original studies andreviews will stimulate the continuing efforts to understandthe molecular pathology underlying PD/parkinsonism, thedevelopment of strategies to treat these conditions, and theevaluation of outcomes.
Acknowledgment
Wewould like to thank the authors and the reviewers for theirexcellent contributions.
Hiroyuki TomiyamaSuzanne LesageEng-King TanBeom S. Jeon
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