Amyloid precursor protein

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Amyloid precursor protein
Properties of human protein
Mass / length primary structure 753 amino acids
Secondary to quaternary structure single pass membrane protein
Isoforms 10
Identifier
Gene name APP
External IDs
Inhibitor classification
MEROPS I02.015
Occurrence
Homology family Beta amyloid
Parent taxon Vertebrates

Cleavage of the APP by α-, β- and γ-secretase (s)

The amyloid precursor protein ( amyloid precursor protein, APP) is an integral membrane protein that takes from the one that in the formation of synapses play a role, although its function is not yet known until now.

When the APP, which has a size of 753-770 amino acid units, is cleaved by the alpha secretases , smaller, water-soluble proteins with 654 to 670 AA building blocks , so-called sAPPs or APPsα , have neuroprotective properties.

When Alzheimer's disease develops, two enzymes , beta-secretase and gamma-secretase , cut a 39 to 42 amino acid long, neurotoxic fragment from the amyloid precursor protein, which is called β-amyloid . This fragment is a major component of the plaques in the brains of Alzheimer's patients.

In humans, the gene for APP is on chromosome 21. This is the reason why people with trisomy 21 (Down's syndrome) often develop Alzheimer's disease at a very young age. All animals have homologs .

Mutations in the APP gene can trigger familial (genetic) Alzheimer's disease or, as in the case of the A673T mutation, prevent the onset of the disease.

Individual evidence

  1. ↑ C. Priller, T. Bauer, G. Mitteregger, B. Krebs, HA Kretzschmar, J. Herms: Synapse formation and function is modulated by the amyloid precursor protein. In: J Neurosci. 26 (27), 2006, pp. 7212-7221. PMID 16822978
  2. ↑ Detlev Ganten, Aloys Greither: Molecular medicine basics of age-specific diseases. Springer-Verlag , 2004, ISBN 3-540-00858-6 .
  3. ↑ T. Matsui, M. Ingelsson, H. Fukumoto, K. Ramasamy, H. Kowa, MP Frosch, MC Irizarry, BT Hyman: Expression of APP pathway mRNAs and proteins in Alzheimer's disease. In: Brain Res Epub. 2007. PMID 17586478
  4. ↑ H. Zheng, EH Koo: The amyloid precursor protein: beyond amyloid. In: Mol Neurodegener. 3; 1, 2006, p. 5. PMID 16930452
  5. ↑ Thorlakur Jonsson, Jasvinder K. Atwal, Stacy Steinberg, Jon Snaedal, Palmi V. Jonsson, Sigurbjorn Bjornsson, Hreinn Stefansson, Patrick Sulem, Daniel Gudbjartsson, Janice Maloney, Kwame Hoyte, Amy Gustafson, Yichin Liu, Yanmei Lu, Tushar Bhangale, Robert R. Graham, Johanna Huttenlocher, Gyda Bjornsdottir, Ole A. Andreassen, Erik G. Jönsson, Aarno Palotie, Timothy W. Behrens, Olafur T. Magnusson, Augustine Kong, Unnur Thorsteinsdottir et al .: A mutation in APP protects against Alzheimer's disease and age-related cognitive decline , Nature Vol. 488, pp. 96-99 (August 2, 2012), doi: 10.1038 / nature11283 ; accessed on May 31, 2016.

literature

  • PJ Barrett, Y. Song, et al. a .: The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. In: Science. Volume 336, Number 6085, June 2012, pp. 1168-1171. doi: 10.1126 / science.1219988 . PMID 22654059 .

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