Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Science Careers Booklet

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 15 April 2004
Science 21 May 2004:
Vol. 304. no. 5674, pp. 1158 - 1160
DOI: 10.1126/science.1096284
Prev | Table of Contents | Next

Reports

Hereditary Early-Onset Parkinson's Disease Caused by Mutations in PINK1

Enza Maria Valente,1*{ddagger} Patrick M. Abou-Sleiman,2* Viviana Caputo,1,3{dagger} Miratul M. K. Muqit,2,4{dagger} Kirsten Harvey,5 Suzana Gispert,6 Zeeshan Ali,6 Domenico Del Turco,7 Anna Rita Bentivoglio,9 Daniel G Healy,2 Alberto Albanese,10 Robert Nussbaum,11 Rafael González-Maldonado,12 Thomas Deller,7 Sergio Salvi,1 Pietro Cortelli,13 William P. Gilks,2 David S. Latchman,4,14 Robert J. Harvey,5 Bruno Dallapiccola,1,3 Georg Auburger,8{ddagger} Nicholas W. Wood2{ddagger}

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.

1 CSS IRCCS, Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy.
2 Department of Molecular Neuroscience, Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
3 Department of Experimental Medicine and Pathology, University La Sapienza, Viale Regina Elena 324, 00187 Rome, Italy.
4 Medical Molecular Biology Unit, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
5 Department of Pharmacology, The School of Pharmacy, 29/39 Brunswick Square, London WC1N 1AX, UK.
6 Institute for Experimental Neurobiology, J.W. Goethe University, Theodor Stern Kai 7, 60590 Frankfurt/M, Germany.
7 Institute of Clinical Neuroanatomy, J.W. Goethe University, Theodor Stern Kai 7, 60590 Frankfurt/M, Germany.
8 Section of Molecular Neurogenetics, Clinic for Neurology; J.W. Goethe University, Theodor Stern Kai 7, 60590 Frankfurt/M, Germany.
9 Institute of Neurology, Catholic University, largo A. Gemelli 8, I-00168 Rome, Italy.
10 National Neurologic Institute Carlo Besta, via Celoria 11, 20133 Milan, Italy.
11 National Human Genetics Research Institute, National Institutes of Health, 49 Convent Drive, Bethesda, MD 20892, USA.
12 Department of Neurology, Hospital Universitatio San Cecilio, Avenida Dr. Olóriz s/n, 18012 Granada, Spain.
13 Department of Neurosciences, University of Modena and Reggio Emilia, via del Pozzo 71, 41100 Modena, Italy.
14 Birkbeck, University of London, Malet Street, London WC1E 7HX, UK.


* These authors contributed equally to this work.

{dagger} These authors share joint second authorship.

{ddagger} To whom correspondence should be addressed. E-mail: n.wood{at}ion.ucl.ac.uk (N.W.W.); auburger{at}em.uni-frankfurt.de (G.A.); e.valente{at}css-mendel.it (E.M.V.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Pink1 regulates mitochondrial dynamics through interaction with the fission/fusion machinery.
Y. Yang, Y. Ouyang, L. Yang, M. F. Beal, A. McQuibban, H. Vogel, and B. Lu (2008)
PNAS 105, 7070-7075
   Abstract »    Full Text »    PDF »
Structural effects of Parkinson's disease linked DJ-1 mutations.
G. Malgieri and D. Eliezer (2008)
Protein Sci. 17, 855-868
   Abstract »    Full Text »    PDF »
High-Throughput Homogeneous Mass Cleave Assay Technology for the Diagnosis of Autosomal Recessive Parkinson's Disease.
C. Schroeder, M. Walter, D. Berg, P. Leitner, P. Bauer, Z. Kohl, J. Winkler, O. Riess, and M. Bonin (2008)
J. Mol. Diagn. 10, 217-224
   Abstract »    Full Text »    PDF »
Mitochondrial Import and Accumulation of {alpha}-Synuclein Impair Complex I in Human Dopaminergic Neuronal Cultures and Parkinson Disease Brain.
L. Devi, V. Raghavendran, B. M. Prabhu, N. G. Avadhani, and H. K. Anandatheerthavarada (2008)
J. Biol. Chem. 283, 9089-9100
   Abstract »    Full Text »    PDF »
{alpha}-Synuclein Aggregates Interfere with Parkin Solubility and Distribution: ROLE IN THE PATHOGENESIS OF PARKINSON DISEASE.
K. Kawahara, M. Hashimoto, P. Bar-On, G. J. Ho, L. Crews, H. Mizuno, E. Rockenstein, S. Z. Imam, and E. Masliah (2008)
J. Biol. Chem. 283, 6979-6987
   Abstract »    Full Text »    PDF »
Pink1 Parkinson mutations, the Cdc37/Hsp90 chaperones and Parkin all influence the maturation or subcellular distribution of Pink1.
A. Weihofen, B. Ostaszewski, Y. Minami, and D. J. Selkoe (2008)
Hum. Mol. Genet. 17, 602-616
   Abstract »    Full Text »    PDF »
Cytoplasmic Pink1 activity protects neurons from dopaminergic neurotoxin MPTP.
M. E. Haque, K. J. Thomas, C. D'Souza, S. Callaghan, T. Kitada, R. S. Slack, P. Fraser, M. R. Cookson, A. Tandon, and D. S. Park (2008)
PNAS 105, 1716-1721
   Abstract »    Full Text »    PDF »
The PINK1/Parkin pathway regulates mitochondrial morphology.
A. C. Poole, R. E. Thomas, L. A. Andrews, H. M. McBride, A. J. Whitworth, and L. J. Pallanck (2008)
PNAS 105, 1638-1643
   Abstract »    Full Text »    PDF »
The role of autophagy-lysosome pathway in neurodegeneration associated with Parkinson's disease.
T. Pan, S. Kondo, W. Le, and J. Jankovic (2008)
Brain
   Abstract »    Full Text »    PDF »
New insights into PTEN.
T. Tamguney and D. Stokoe (2007)
J. Cell Sci. 120, 4071-4079
   Abstract »    Full Text »    PDF »
Parkinson disease, 10 years after its genetic revolution: Multiple clues to a complex disorder.
C. Klein and M. G. Schlossmacher (2007)
Neurology 69, 2093-2104
   Abstract »    Full Text »    PDF »
Loss-of-Function of Human PINK1 Results in Mitochondrial Pathology and Can Be Rescued by Parkin.
N. Exner, B. Treske, D. Paquet, K. Holmstrom, C. Schiesling, S. Gispert, I. Carballo-Carbajal, D. Berg, H.-H. Hoepken, T. Gasser, et al. (2007)
J. Neurosci. 27, 12413-12418
   Abstract »    Full Text »    PDF »
Profiling Phosphoproteins of Yeast Mitochondria Reveals a Role of Phosphorylation in Assembly of the ATP Synthase.
J. Reinders, K. Wagner, R. P. Zahedi, D. Stojanovski, B. Eyrich, M. van der Laan, P. Rehling, A. Sickmann, N. Pfanner, and C. Meisinger (2007)
Mol. Cell. Proteomics 6, 1896-1906
   Abstract »    Full Text »    PDF »
Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration?.
C. Scheele, A. R. Nielsen, T. B. Walden, D. A. Sewell, C. P. Fischer, R. J. Brogan, N. Petrovic, O. Larsson, P. A. Tesch, K. Wennmalm, et al. (2007)
FASEB J 21, 3653-3665
   Abstract »    Full Text »    PDF »
The Roles of Kinases in Familial Parkinson's Disease.
M. R. Cookson, W. Dauer, T. Dawson, E. A. Fon, M. Guo, and J. Shen (2007)
J. Neurosci. 27, 11865-11868
   Abstract »    Full Text »    PDF »
Parkinson's disease.
B. Thomas and M. F. Beal (2007)
Hum. Mol. Genet. 16, R183-R194
   Abstract »    Full Text »    PDF »
Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease.
P. T. Luoma, J. Eerola, S. Ahola, A. H. Hakonen, O. Hellstrom, K. T. Kivisto, P. J. Tienari, and A. Suomalainen (2007)
Neurology 69, 1152-1159
   Abstract »    Full Text »    PDF »
Impairment of the Ubiquitin-Proteasome Pathway Is a Downstream Endoplasmic Reticulum Stress Response Induced by Extracellular Human Islet Amyloid Polypeptide and Contributes to Pancreatic {beta}-Cell Apoptosis.
S. Casas, R. Gomis, F. M. Gribble, J. Altirriba, S. Knuutila, and A. Novials (2007)
Diabetes 56, 2284-2294
   Abstract »    Full Text »    PDF »
Physiology versus pathology in Parkinson's disease.
K. Nakamura and R. H. Edwards (2007)
PNAS 104, 11867-11868
   Full Text »    PDF »
From the Cover: Impaired dopamine release and synaptic plasticity in the striatum of PINK1-deficient mice.
T. Kitada, A. Pisani, D. R. Porter, H. Yamaguchi, A. Tscherter, G. Martella, P. Bonsi, C. Zhang, E. N. Pothos, and J. Shen (2007)
PNAS 104, 11441-11446
   Abstract »    Full Text »    PDF »
PINK1, a gene product of PARK6, accumulates in {alpha}-synucleinopathy brains.
T. Murakami, Y. Moriwaki, T. Kawarabayashi, M. Nagai, Y. Ohta, K. Deguchi, T. Kurata, N. Morimoto, Y. Takehisa, E. Matsubara, et al. (2007)
J. Neurol. Neurosurg. Psychiatry 78, 653-654
   Full Text »    PDF »
Apoptotic mechanisms in mutant LRRK2-mediated cell death.
C. Iaccarino, C. Crosio, C. Vitale, G. Sanna, M. T. Carri, and P. Barone (2007)
Hum. Mol. Genet. 16, 1319-1326
   Abstract »    Full Text »    PDF »
Nonparametric estimation of age-at-onset distributions from censored kin-cohort data.
Y. Wang, L. N. Clark, K. Marder, and D. Rabinowitz (2007)
Biometrika 94, 403
   Abstract »    Full Text »    PDF »
Genetic enhancement of cognition in a kindred with cone-rod dystrophy due to RIMS1 mutation.
S. M Sisodiya, P. J Thompson, A. Need, S. E Harris, M. E Weale, S. E Wilkie, M. Michaelides, S. L Free, N. Walley, C. Gumbs, et al. (2007)
J. Med. Genet. 44, 373-380
   Abstract »    Full Text »    PDF »
Merging Mouse Transcriptome Analyses with Parkinson's Disease Linkage Studies.
D. Gherbassi, L. Bhatt, S. Thuret, and H. H. Simon (2007)
DNA Res
   Abstract »    Full Text »    PDF »
A cell biological perspective on mitochondrial dysfunction in Parkinson disease and other neurodegenerative diseases.
W. Mandemakers, V. A. Morais, and B. De Strooper (2007)
J. Cell Sci. 120, 1707-1716
   Abstract »    Full Text »    PDF »
Leucine-rich repeat kinase 2 associates with lipid rafts.
T. Hatano, S.-i. Kubo, S. Imai, M. Maeda, K. Ishikawa, Y. Mizuno, and N. Hattori (2007)
Hum. Mol. Genet. 16, 678-690
   Abstract »    Full Text »    PDF »
Emerging Roles for Ubiquitin and Protein Degradation in Neuronal Function.
J. J. Yi and M. D. Ehlers (2007)
Pharmacol. Rev. 59, 14-39
   Abstract »    Full Text »    PDF »
PINK1 mutation heterozygosity and the risk of Parkinson's disease.
M Toft, R Myhre, L Pielsticker, L R White, J O Aasly, and M J Farrer (2007)
J. Neurol. Neurosurg. Psychiatry 78, 82-84
   Abstract »    Full Text »    PDF »
Narrative review: protein degradation and human diseases: the ubiquitin connection..
E. Reinstein and A. Ciechanover (2006)
Ann Intern Med 145, 676-684
   Abstract »    Full Text »    PDF »
C-terminal truncation and Parkinson's disease-associated mutations down-regulate the protein serine/threonine kinase activity of PTEN-induced kinase-1.
C. H. Sim, D. S. S. Lio, S. S. Mok, C. L. Masters, A. F. Hill, J. G. Culvenor, and H.-C. Cheng (2006)
Hum. Mol. Genet. 15, 3251-3262
   Abstract »    Full Text »    PDF »
T313M PINK1 Mutation in an Extended Highly Consanguineous Saudi Family With Early-Onset Parkinson Disease..
M. A. Chishti, S. Bohlega, M. Ahmed, A. Loualich, P. Carroll, C. Sato, P. St George-Hyslop, D. Westaway, and E. Rogaeva (2006)
Arch Neurol 63, 1483-1485
   Abstract »    Full Text »    PDF »
From the Cover: Antioxidants protect PINK1-dependent dopaminergic neurons in Drosophila.
D. Wang, L. Qian, H. Xiong, J. Liu, W. S. Neckameyer, S. Oldham, K. Xia, J. Wang, R. Bodmer, and Z. Zhang (2006)
PNAS 103, 13520-13525
   Abstract »    Full Text »    PDF »
Genetic testing in Parkinson disease: promises and pitfalls..
E.-K. Tan and J. Jankovic (2006)
Arch Neurol 63, 1232-1237
   Full Text »    PDF »
Juvenile-Onset Parkinsonism as a Result of the First Mutation in the Adenosine Triphosphate Orientation Domain of PINK1..
A.-L. Leutenegger, M. A. M. Salih, P. Ibanez, M. M. Mukhtar, S. Lesage, A. Arabi, E. Lohmann, A. Durr, A. E. M. Ahmed, and A. Brice (2006)
Arch Neurol 63, 1257-1261
   Abstract »    Full Text »    PDF »
Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging.
M. C. Meulener, K. Xu, L. Thomson, H. Ischiropoulos, and N. M. Bonini (2006)
PNAS 103, 12517-12522
   Abstract »    Full Text »    PDF »
Mitochondrial pathology and muscle and dopaminergic neuron degeneration caused by inactivation of Drosophila Pink1 is rescued by Parkin.
Y. Yang, S. Gehrke, Y. Imai, Z. Huang, Y. Ouyang, J.-W. Wang, L. Yang, M. F. Beal, H. Vogel, and B. Lu (2006)
PNAS 103, 10793-10798
   Abstract »    Full Text »    PDF »
PINK1 protein in normal human brain and Parkinson's disease.
S. Gandhi, M. M. K. Muqit, L. Stanyer, D. G. Healy, P. M. Abou-Sleiman, I. Hargreaves, S. Heales, M. Ganguly, L. Parsons, A. J. Lees, et al. (2006)
Brain 129, 1720-1731
   Abstract »    Full Text »    PDF »
The sepiapterin reductase gene region reveals association in the PARK3 locus: analysis of familial and sporadic Parkinson's disease in European populations.
M Sharma, J C Mueller, A Zimprich, P Lichtner, A Hofer, P Leitner, S Maass, D Berg, A Durr, V Bonifati, et al. (2006)
J. Med. Genet. 43, 557-562
   Abstract »    Full Text »    PDF »
Increased risk for heterozygotes in recessive Parkinson disease..
U. Beffert and R. N. Rosenberg (2006)
Arch Neurol 63, 807-808
   Full Text »    PDF »
Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study..
M. Sun, J. C. Latourelle, G. F. Wooten, M. F. Lew, C. Klein, H. A. Shill, L. I. Golbe, M. H. Mark, B. A. Racette, J. S. Perlmutter, et al. (2006)
Arch Neurol 63, 826-832
   Abstract »    Full Text »    PDF »
Clinical spectrum of homozygous and heterozygous PINK1 mutations in a large German family with Parkinson disease: role of a single hit?.
K. Hedrich, J. Hagenah, A. Djarmati, A. Hiller, T. Lohnau, K. Lasek, A. Grunewald, R. Hilker, S. Steinlechner, H. Boston, et al. (2006)
Arch Neurol 63, 833-838
   Abstract »    Full Text »    PDF »
Association of PINK1 and DJ-1 confers digenic inheritance of early-onset Parkinson's disease.
B. Tang, H. Xiong, P. Sun, Y. Zhang, D. Wang, Z. Hu, Z. Zhu, H. Ma, Q. Pan, J.-h. Xia, et al. (2006)
Hum. Mol. Genet. 15, 1816-1825
   Abstract »    Full Text »    PDF »
Etiology of Parkinson's disease.
A. H.V. Schapira (2006)
Neurology 66, S10-S23
   Abstract »    Full Text »
Direct evidence for coherent low velocity axonal transport of mitochondria.
K. E. Miller and M. P. Sheetz (2006)
J. Cell Biol. 173, 373-381
   Abstract »    Full Text »    PDF »
Mitochondria in Parkinson disease: back in fashion with a little help from genetics..
M. M. K. Muqit, S. Gandhi, and N. W. Wood (2006)
Arch Neurol 63, 649-654
   Abstract »    Full Text »    PDF »
Reactive Oxygen Species-Mediated Mitochondria-to-Nucleus Signaling: A Key to Aging and Radical-Caused Diseases.
P. Storz (2006)
Sci. STKE 2006, re3
   Abstract »    Full Text »    PDF »
Multiple candidate gene analysis identifies {alpha}-synuclein as a susceptibility gene for sporadic Parkinson's disease.
I. Mizuta, W. Satake, Y. Nakabayashi, C. Ito, S. Suzuki, Y. Momose, Y. Nagai, A. Oka, H. Inoko, J. Fukae, et al. (2006)
Hum. Mol. Genet. 15, 1151-1158
   Abstract »    Full Text »    PDF »
Case-control study of the parkin gene in early-onset Parkinson disease..
L. N. Clark, S. Afridi, E. Karlins, Y. Wang, H. Mejia-Santana, J. Harris, E. D. Louis, L. J. Cote, H. Andrews, S. Fahn, et al. (2006)
Arch Neurol 63, 548-552
   Abstract »    Full Text »    PDF »
A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease.
The NINDS NET-PD Investigators (2006)
Neurology 66, 664-671
   Abstract »    Full Text »    PDF »
Implications of genetics on the diagnosis and care of patients with Parkinson disease..
C. Klein (2006)
Arch Neurol 63, 328-334
   Abstract »    Full Text »    PDF »
Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa.
P. Ibanez, S. Lesage, E. Lohmann, S. Thobois, G. D. Michele, M. Borg, Y. Agid, A. Durr, A. Brice, and and the French Parkinson's Disease Genetics Study (2006)
Brain 129, 686-694
   Abstract »    Full Text »    PDF »
Mitochondrial Reactive Oxygen Species in Mice Lacking Superoxide Dismutase 2: ATTENUATION VIA ANTIOXIDANT TREATMENT.
K. J. Morten, B. A. C. Ackrell, and S. Melov (2006)
J. Biol. Chem. 281, 3354-3359
   Abstract »    Full Text »    PDF »
Parkin Ubiquitinates and Promotes the Degradation of RanBP2.
J. W. Um, D. S. Min, H. Rhim, J. Kim, S. R. Paik, and K. C. Chung (2006)
J. Biol. Chem. 281, 3595-3603
   Abstract »    Full Text »    PDF »
Heterogeneous Phenotype in a Family With Compound Heterozygous Parkin Gene Mutations.
H. Deng, W.-D. Le, C. B. Hunter, W. G. Ondo, Y. Guo, W.-J. Xie, and J. Jankovic (2006)
Arch Neurol 63, 273-277
   Abstract »    Full Text »    PDF »
The Parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity.
C. J. Gloeckner, N. Kinkl, A. Schumacher, R. J. Braun, E. O'Neill, T. Meitinger, W. Kolch, H. Prokisch, and M. Ueffing (2006)
Hum. Mol. Genet. 15, 223-232
   Abstract »    Full Text »    PDF »
Similar Patterns of Mitochondrial Vulnerability and Rescue Induced by Genetic Modification of {alpha}-Synuclein, Parkin, and DJ-1 in Caenorhabditis elegans.
R. Ved, S. Saha, B. Westlund, C. Perier, L. Burnam, A. Sluder, M. Hoener, C. M. P. Rodrigues, A. Alfonso, C. Steer, et al. (2005)
J. Biol. Chem. 280, 42655-42668
   Abstract »    Full Text »    PDF »
Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism.
L. Silvestri, V. Caputo, E. Bellacchio, L. Atorino, B. Dallapiccola, E. M. Valente, and G. Casari (2005)
Hum. Mol. Genet. 14, 3477-3492
   Abstract »    Full Text »    PDF »
From The Cover: Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity.
A. B. West, D. J. Moore, S. Biskup, A. Bugayenko, W. W. Smith, C. A. Ross, V. L. Dawson, and T. M. Dawson (2005)
PNAS 102, 16842-16847
   Abstract »    Full Text »    PDF »
Mutational screening of the parkin gene among South Indians with early onset Parkinson's disease.
R H Madegowda, A Kishore, and A Anand (2005)
J. Neurol. Neurosurg. Psychiatry 76, 1588-1590
   Abstract »    Full Text »    PDF »
Partial Mitochondrial Inhibition Causes Striatal Dopamine Release Suppression and Medium Spiny Neuron Depolarization via H2O2 Elevation, Not ATP Depletion.
L. Bao, M. V. Avshalumov, and M. E. Rice (2005)
J. Neurosci. 25, 10029-10040
   Abstract »    Full Text »    PDF »
Wild-type PINK1 Prevents Basal and Induced Neuronal Apoptosis, a Protective Effect Abrogated by Parkinson Disease-related Mutations.
A. Petit, T. Kawarai, E. Paitel, N. Sanjo, M. Maj, M. Scheid, F. Chen, Y. Gu, H. Hasegawa, S. Salehi-Rad, et al. (2005)
J. Biol. Chem. 280, 34025-34032
   Abstract »    Full Text »    PDF »
Molecular pathogenesis of Parkinson's disease.
S. Gandhi and N. W. Wood (2005)
Hum. Mol. Genet. 14, 2749-2755
   Abstract »    Full Text »    PDF »
LRRK2 gene in Parkinson disease: Mutation analysis and case control association study.
C. Paisan-Ruiz, A. E. Lang, T. Kawarai, C. Sato, S. Salehi-Rad, G. K. Fisman, T. Al-Khairallah, P. St George-Hyslop, A. Singleton, and E. Rogaeva (2005)
Neurology 65, 696-700
   Abstract »    Full Text »    PDF »
Accumulation of the Authentic Parkin Substrate Aminoacyl-tRNA Synthetase Cofactor, p38/JTV-1, Leads to Catecholaminergic Cell Death.
H. S. Ko, R. von Coelln, S. R. Sriram, S. W. Kim, K. K. K. Chung, O. Pletnikova, J. Troncoso, B. Johnson, R. Saffary, E. L. Goh, et al. (2005)
J. Neurosci. 25, 7968-7978
   Abstract »    Full Text »    PDF »
Neurodegenerative disorders: Parkinson's disease and Huntington's disease.
S M Hague, S Klaffke, and O Bandmann (2005)
J. Neurol. Neurosurg. Psychiatry 76, 1058-1063
   Abstract »    Full Text »    PDF »
Gene Expression Profiling of Sporadic Parkinson's Disease Substantia Nigra Pars Compacta Reveals Impairment of Ubiquitin-Proteasome Subunits, SKP1A, Aldehyde Dehydrogenase, and Chaperone HSC-70.
S. MANDEL, E. GRUNBLATT, P. RIEDERER, N. AMARIGLIO, J. JACOB-HIRSCH, G. RECHAVI, and M. B. H. YOUDIM (2005)
Ann. N.Y. Acad. Sci. 1053, 356-375
   Abstract »    Full Text »    PDF »
Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson's disease.
K. M. Strauss, L. M. Martins, H. Plun-Favreau, F. P. Marx, S. Kautzmann, D. Berg, T. Gasser, Z. Wszolek, T. Muller, A. Bornemann, et al. (2005)
Hum. Mol. Genet. 14, 2099-2111
   Abstract »    Full Text »    PDF »
Parkin negatively regulates JNK pathway in the dopaminergic neurons of Drosophila.
G.-H. Cha, S. Kim, J. Park, E. Lee, M. Kim, S. B. Lee, J. M. Kim, J. Chung, and K. S. Cho (2005)
PNAS 102, 10345-10350
   Abstract »    Full Text »    PDF »
Mitochondrial localization of the Parkinson's disease related protein DJ-1: implications for pathogenesis.
L. Zhang, M. Shimoji, B. Thomas, D. J. Moore, S.-W. Yu, N. I. Marupudi, R. Torp, I. A. Torgner, O. P. Ottersen, T. M. Dawson, et al. (2005)
Hum. Mol. Genet. 14, 2063-2073
   Abstract »    Full Text »    PDF »
Early-onset parkinsonism associated with PINK1 mutations: Frequency, genotypes, and phenotypes.
V. Bonifati, C. F. Rohe, G. J. Breedveld, E. Fabrizio, M. De Mari, C. Tassorelli, A. Tavella, R. Marconi, D. J. Nicholl, H. F. Chien, et al. (2005)
Neurology 65, 87-95
   Abstract »    Full Text »    PDF »
Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death.
E. Junn, H. Taniguchi, B. S. Jeong, X. Zhao, H. Ichijo, and M. M. Mouradian (2005)
PNAS 102, 9691-9696
   Abstract »    Full Text »    PDF »
Cell type-specific gene expression of midbrain dopaminergic neurons reveals molecules involved in their vulnerability and protection.
C. Y. Chung, H. Seo, K. C. Sonntag, A. Brooks, L. Lin, and O. Isacson (2005)
Hum. Mol. Genet. 14, 1709-1725
   Abstract »    Full Text »    PDF »
Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism.
Y. Li, H. Tomiyama, K. Sato, Y. Hatano, H. Yoshino, M. Atsumi, M. Kitaguchi, S. Sasaki, S. Kawaguchi, H. Miyajima, et al. (2005)
Neurology 64, 1955-1957
   Abstract »    Full Text »    PDF »
The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease.
A. Albanese, E. M. Valente, L. M. Romito, E. Bellacchio, A. E. Elia, and B. Dallapiccola (2005)
Neurology 64, 1958-1960
   Abstract »    Full Text »    PDF »
Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability.
A. Beilina, M. Van Der Brug, R. Ahmad, S. Kesavapany, D. W. Miller, G. A. Petsko, and M. R. Cookson (2005)
PNAS 102, 5703-5708
   Abstract »    Full Text »    PDF »
GDAP1, the protein causing Charcot-Marie-Tooth disease type 4A, is expressed in neurons and is a