α-synuclein
Α-synuclein | ||
---|---|---|
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 (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:
- Amino acids 1-60: The characteristic of this N-terminal , amphipathic section is a sequence of eleven amino acids which is repeated four times. What these sections have in common is that they each have the consensus sequence KTKEGV. The resulting secondary structure of this sequence is an α-helix , it resembles domains that bind to apolipoproteins .
- Amino acids 61–95: This section is hydrophobic and has the so-called non-amyloid-β component (NAC) region, which is involved in protein aggregation. There are also three more KTKEGV repetitions.
- Amino acids 96–140: In this section you can find many amino acids with an acidic residue but also proline . This C-terminal section shows no tendency to form any particular secondary structure .
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
swell
- ↑ Homologues to P37840 at OMA
- ↑ 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).
- ↑ 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 ]).
- ↑ UniProt P37840
- ↑ ( Page no longer available , search in web archives: Pathway DB: Alpha-synuclein signaling. )
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ↑ 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 .
- ^ 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).
- ↑ 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).
- ↑ 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 .
- ↑ Thomas H. Maugh: First trial of vaccine to treat Parkinson's disease begins. In: Los Angeles Times. June 7, 2012, accessed June 11, 2012 .