α-synuclein

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Α-synuclein
Α-synuclein

Existing structural data : 1XQ8

Properties of human protein
Mass / length primary structure 140 amino acids
Secondary to quaternary structure Monomer
Isoforms 3
Identifier
Gene name SNCA
External IDs
Transporter classification
TCDB 1.C.77.1.1
designation Synuclein family
Occurrence
Parent taxon Vertebrates

α-Synuclein staining of a Lewy body in the substantia nigra in Parkinson's disease.

α-synuclein (including α-synuclein, SNCA) is a small, soluble protein in the brain of vertebrates , inter alia, the dopamine regulates -Ausschüttung. It is able to form membrane channels and is therefore a transport protein . Mutations in SNCA - gene responsible for synucleinopathies how the hereditary forms 1 and 4 of Parkinson's disease and Lewy body dementia .

function

As the name implies, SNCA was initially identified as a synaptic and nuclear protein. Despite intensive studies, the exact role of SNCA is not yet clearly defined: there is evidence that SNCA plays a role in maintaining the synaptic pool of vesicles and modulating dopamine release, but SNCA knockout mice have no apparent phenotype.

Primary structure

The primary structure of α-synuclein is divided into three different domains:

pathology

α-Synuclein has been identified in the human brain as a precursor of the non-amyloid β protein . Scientists at the US National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) in Bethesda , Maryland found in 1997 that it is involved in several pathogenic processes in neurodegenerative diseases such as Parkinson 's disease . A positive immune reaction for antibodies against α-synuclein was found in the Lewy bodies typical of the latter . This protein is said to have a toxic effect on certain nerve cells, but above all on dopaminergic neurons of the substantia nigra , in which it is seen in the form of protofibrils as a contributor to oxidative stress and the resulting neuronal cell death. The importance of α-synucleins in the development of prion diseases or Alzheimer's disease is also discussed.

The group of neurodegenerative diseases in which there is a pathological accumulation of α-synuclein in the central nervous system are known as synucleinopathies .

The Viennese company AFFiRiS AG has been conducting a clinical study with the active ingredient PD01A directed against α-synuclein since June 5, 2012 with the aim of developing a vaccine against Parkinson's disease . The vaccination is intended to stimulate the immune system to produce antibodies against α-synuclein.

literature

  • MH Polymeropoulos, C. Lavedan, E. Leroy et al .: Mutation in the alpha-synuclein gene identified in families with Parkinson's disease . In: Science . tape 276 , no. 5321 , June 1997, p. 2045-2047 , doi : 10.1126 / science.276.5321.2045 , PMID 9197268 .
  • Manuela Neumann, Philipp J. Kahle, Benoit I. Giasson et al .: Misfolded proteinase K-resistant hyperphosphorylated alpha-synuclein in aged transgenic mice with locomotor deterioration and in human alpha-synucleinopathies . In: The Journal of Clinical Investigation . tape 110 , no. 10 , November 2002, ISSN  0021-9738 , p. 1429-1439 , doi : 10.1172 / JCI15777 , PMID 12438441 , PMC 151810 (free full text).
  • Sandra Blakeslee: In Folding Proteins, Clues to Many Diseases . In: The New York Times . May 21, 2002 ( nytimes.com ).
  • Ahmad Jowaed, Ina Schmitt, Oliver Kaut, Ullrich Wüllner: Methylation regulates alpha-synuclein expression and is decreased in Parkinson's disease patients' brains . In: The Journal of Neuroscience . tape 30 , no. May 18 , 2010, ISSN  1529-2401 , p. 6355-6359 , doi : 10.1523 / JNEUROSCI.6119-09.2010 , PMID 20445061 .
  • Kelvin C. Luk, Victoria Kehm, Jenna Carroll, Bin Zhang, Patrick O'Brien, John Q. Trojanowski, Virginia M.-Y. Lee: Pathological α-Synuclein Transmission Initiates Parkinson-like Neurodegeneration in Non-transgenic Mice . In: Science . tape 338 , no. 6109 , 2012, p. 949-953 , doi : 10.1126 / science.1227157 , PMID 23161999 , PMC 3552321 (free full text).

Web links

Commons : alpha synuclein  - collection of images, videos and audio files

swell

  1. ↑ Homologues to P37840 at OMA
  2. ↑ Julia M. George: The synucleins . In: Genome Biology . tape 3 , no. 1 , 2002, p. reviews3002.1 – reviews3002.6 , PMID 11806835 , PMC 150459 (free full text).
  3. ↑ C. Lavedan: The synuclein family . In: Genome Research . tape 8 , no. 9 , September 1998, pp. 871-880 , doi : 10.1101 / gr.8.9.871 , PMID 9750188 ( genome.org [PDF; 188 kB ]).
  4. ↑ UniProt P37840
  5. ↑ ( Page no longer available , search in web archives: Pathway DB: Alpha-synuclein signaling. )@1@ 2Template: Dead Link / pid.nci.nih.gov
  6. ↑ L. Maroteaux, JT Campanelli, RH Scheller: Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal . In: The Journal of Neuroscience . tape 8 , no. 8 , August 1988, ISSN  0270-6474 , p. 2804-2815 , PMID 3411354 .
  7. ↑ A. Abeliovich, Y. Schmitz, I. Fariñas, D. Choi-Lundberg, WH Ho, PE Castillo, N. Shinsky, JM Verdugo, M. Armanini, A. Ryan, M. Hynes, H. Phillips, D. Sulzer, A. Rosenthal: Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system . In: Neuron . tape 25 , no. 1 , January 2000, p. 239-252 , PMID 10707987 .
  8. ↑ DD Murphy, SM Rueter, JQ Trojanowski, VM Lee: Synucleins are developmentally expressed, and alpha-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons . In: The Journal of Neuroscience . tape 20 , no. May 9 , 2000, ISSN  1529-2401 , pp. 3214-3220 , PMID 10777786 .
  9. ↑ Leonid Breydo, Jessica W. Wu, Vladimir N. Uversky:-synuclein misfolding and Parkinson's disease . In: Biochimica Et Biophysica Acta . tape 1822 , no. 2 , February 2012, ISSN  0006-3002 , p. 261-285 , doi : 10.1016 / j.bbadis.2011.10.002 , PMID 22024360 .
  10. ^ A. Brunn: Lecture General Pathology. Department of Neuropathology, University of Cologne, summer semester 2005. Medizin.uni-koeln.de ( Memento from April 24, 2009 in the Internet Archive ) (PDF).
  11. ↑ M. Tolnay: α-Synuclein and tau: abnormal protein deposits in Parkinson's (plus) syndrome. In: Switzerland. Arch. Neurol. Psychiatr. Volume 151, 2000, pp. 136-145 ( sanp.ch PDF).
  12. ↑ Parkinson's vaccine - the world's first clinical study in Vienna. AFFiRiS AG, June 5, 2012, archived from the original on June 11, 2012 ; Retrieved June 11, 2012 .
  13. ↑ Thomas H. Maugh: First trial of vaccine to treat Parkinson's disease begins. In: Los Angeles Times. June 7, 2012, accessed June 11, 2012 .