Tags

Type your tag names separated by a space and hit enter

Mendelian forms of Parkinson's disease.
Biochim Biophys Acta. 2009 Jul; 1792(7):587-96.BB

Abstract

Over the last few years, genetic findings have changed our views on Parkinson's disease (PD), as mutations in a growing number of genes are found to cause monogenic forms of the disorder. Point mutations in the gene for alpha-synuclein, as well as duplications and triplications of the wild-type gene cause a dominant form of PD in rare families, pointing towards mishandling of this protein as a crucial step in the molecular pathogenesis of the disorder. Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) have recently been identified as a much more common cause for dominant PD, while mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 all cause autosomal-recessive parkinsonism of early onset. Mutations in recessive genes probably are pathogenic through loss-of-function mechanisms, suggesting that their wild-type products protect dopaminergic cells against a variety of insults. Evidence is emerging that at least some of these genes may play a direct role in the etiology of the common sporadic form of PD. Further, it is likely that the cellular pathways identified in rare monogenic variants of the disease also shed light on the molecular pathogenesis in typical sporadic PD.

Links

  • Publisher Full Text

    • Authors+Show Affiliations

    Gasser T
    Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. thomas.gasser@med.uni-tuebingen.de

    MeSH

    HumansIntracellular Signaling Peptides and ProteinsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2MutationOncogene ProteinsParkinsonian DisordersProtein Deglycase DJ-1Protein KinasesProtein-Serine-Threonine KinasesUbiquitin-Protein Ligasesalpha-Synuclein

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    19168133

    Citation

    Gasser, Thomas. "Mendelian Forms of Parkinson's Disease." Biochimica Et Biophysica Acta, vol. 1792, no. 7, 2009, pp. 587-96.
    Gasser T. Mendelian forms of Parkinson's disease. Biochim Biophys Acta. 2009;1792(7):587-96.
    Gasser, T. (2009). Mendelian forms of Parkinson's disease. Biochimica Et Biophysica Acta, 1792(7), 587-96. https://doi.org/10.1016/j.bbadis.2008.12.007
    Gasser T. Mendelian Forms of Parkinson's Disease. Biochim Biophys Acta. 2009;1792(7):587-96. PubMed PMID: 19168133.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mendelian forms of Parkinson's disease. A1 - Gasser,Thomas, Y1 - 2009/01/06/ PY - 2008/10/31/received PY - 2008/12/23/revised PY - 2008/12/24/accepted PY - 2009/1/27/entrez PY - 2009/1/27/pubmed PY - 2009/8/26/medline SP - 587 EP - 96 JF - Biochimica et biophysica acta JO - Biochim. Biophys. Acta VL - 1792 IS - 7 N2 - Over the last few years, genetic findings have changed our views on Parkinson's disease (PD), as mutations in a growing number of genes are found to cause monogenic forms of the disorder. Point mutations in the gene for alpha-synuclein, as well as duplications and triplications of the wild-type gene cause a dominant form of PD in rare families, pointing towards mishandling of this protein as a crucial step in the molecular pathogenesis of the disorder. Mutations in the gene for leucine-rich repeat kinase 2 (LRRK2) have recently been identified as a much more common cause for dominant PD, while mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 all cause autosomal-recessive parkinsonism of early onset. Mutations in recessive genes probably are pathogenic through loss-of-function mechanisms, suggesting that their wild-type products protect dopaminergic cells against a variety of insults. Evidence is emerging that at least some of these genes may play a direct role in the etiology of the common sporadic form of PD. Further, it is likely that the cellular pathways identified in rare monogenic variants of the disease also shed light on the molecular pathogenesis in typical sporadic PD. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/19168133/Mendelian_forms_of_Parkinson's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(08)00270-6 DB - PRIME DP - Unbound Medicine ER -