For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
19
views
58
references
 Top references
cited by
69
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      906
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application

      review-article
      Author(s): , *
      Publication date (Electronic):
      Journal: Parkinson's Disease
      Publisher: Hindawi Publishing Corporation

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism of α-synuclein in Parkinson's disease remains obscure. Recent research showed that various α-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson's disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction of α-synuclein associated with Parkinson's disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target.

          Related collections

          Most cited references58

          • Record: found
          • Abstract: found
          • Article: not found

          Accelerated in vitro fibril formation by a mutant alpha-synuclein linked to early-onset Parkinson disease.

          K. A. Conway, J Harper, P. Lansbury (1998)
          Two mutations in the gene encoding alpha-synuclein have been linked to early-onset Parkinson's disease (PD). alpha-Synuclein is a component of Lewy bodies, the fibrous cytoplasmic inclusions characteristic of nigral dopaminergic neurons in the PD brain. This connection between genetics and pathology suggests that the alpha-synuclein mutations may promote PD pathogenesis by accelerating Lewy body formation. To test this, we studied alpha-synuclein folding and aggregation in vitro, in the absence of other Lewy body-associated molecules. We demonstrate here that both mutant forms of alpha-synuclein (A53T and A30P) are, like wild-type alpha-synuclein (WT), disordered in dilute solution. However, at higher concentrations, Lewy body-like fibrils and discrete spherical assemblies are formed; most rapidly by A53T. Thus, mutation-induced acceleration of alpha-synuclein fibril formation may contribute to the early onset of familial PD.
          Article 0 comments Cited 319 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            G51D α-synuclein mutation causes a novel parkinsonian-pyramidal syndrome.

            Suzanne Lesage, Mathieu Anheim, Franck Letournel … (2013)
            To date, 3 rare missense mutations in the SNCA (α-synuclein) gene and the more frequent duplications or triplications of the wild-type gene are known to cause a broad array of clinical and pathological symptoms in familial Parkinson disease (PD). Here, we describe a French family with a parkinsonian-pyramidal syndrome harboring a novel heterozygous SNCA mutation. Whole exome sequencing of DNA from 3 patients in a 3-generation pedigree was used to identify a new PD-associated mutation in SNCA. Clinical and pathological features of the patients were analyzed. The cytotoxic effects of the mutant and wild-type proteins were assessed by analytical ultracentrifugation, thioflavin T binding, transmission electron microscopy, cell viability assay, and caspase-3 activation. We identified a novel SNCA G51D (c.152 G>A) mutation that cosegregated with the disease and was absent from controls. G51D was associated with an unusual PD phenotype characterized by early disease onset, moderate response to levodopa, rapid progression leading to loss of autonomy and death within a few years, marked pyramidal signs including bilateral extensor plantar reflexes, occasionally spasticity, and frequently psychiatric symptoms. Pathological lesions predominated in the basal ganglia and the pyramidal tracts and included fine, diffuse cytoplasmic inclusions containing phospho-α-synuclein in superficial layers of the cerebral cortex, including the entorhinal cortex. Functional studies showed that G51D α-synuclein oligomerizes more slowly and its fibrils are more toxic than those of the wild-type protein. We have identified a novel SNCA G51D mutation that causes a form of PD with unusual clinical, neuropathological, and biochemical features. Copyright © 2013 American Neurological Association.
            Article 0 comments Cited 276 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.

              A Abeliovich, Y Schmitz, I Farinas … (2000)
              alpha-Synuclein (alpha-Syn) is a 14 kDa protein of unknown function that has been implicated in the pathophysiology of Parkinson's disease (PD). Here, we show that alpha-Syn-/- mice are viable and fertile, exhibit intact brain architecture, and possess a normal complement of dopaminergic cell bodies, fibers, and synapses. Nigrostriatal terminals of alpha-Syn-/- mice display a standard pattern of dopamine (DA) discharge and reuptake in response to simple electrical stimulation. However, they exhibit an increased release with paired stimuli that can be mimicked by elevated Ca2+. Concurrent with the altered DA release, alpha-Syn-/- mice display a reduction in striatal DA and an attenuation of DA-dependent locomotor response to amphetamine. These findings support the hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission.
              Article 0 comments Cited 268 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Parkinsons Dis
                Journal ID (iso-abbrev): Parkinsons Dis
                Journal ID (publisher-id): PD
                Title: Parkinson's Disease
                Publisher: Hindawi Publishing Corporation
                ISSN (Print): 2090-8083
                ISSN (Electronic): 2042-0080
                Publication date (Print): 2016
                Publication date (Electronic): 17 August 2016
                Volume: 2016
                Electronic Location Identifier: 1720621
                Affiliations
                Department of Neurology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China
                Author notes

                Academic Editor: Shu Wen

                Author information
                http://orcid.org/0000-0002-9635-2056
                http://orcid.org/0000-0001-9473-693X
                Article
                DOI: 10.1155/2016/1720621
                PMC ID: 5005546
                PubMed ID: 27610264
                SO-VID: 337d4716-22cf-4b79-b283-1b726d0d573d
                Copyright © Copyright © 2016 L. Xu and J. Pu.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 15 April 2016
                Date revision received : 3 July 2016
                Date accepted : 10 July 2016
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81400933
                Funded by: Zhejiang Medical Science and Technology Plan Project
                Award ID: 2016KYB119
                Categories
                Subject: Review Article

                ScienceOpen disciplines: Neurology
                Data availability:
                ScienceOpen disciplines: Neurology

                Comments

                Comment on this article

                scite_

                Similar content906

                See all similar

                Cited by66

                See all cited by

                Most referenced authors1,866

                See all reference authors