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ADAM10

Synonyms: ADAM-10, AD10, MADM, HsT18717, A Disintegrin and Metalloproteinase10, CD156c

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ADAM10 stands for A Disintegrin and Metalloproteinase 10. This membrane protein is a sheddase and thought to be the physiological α-secretase for the amyloid precursor protein (APP). In contrast to cleavage by β-secretase, ADAM10-mediated processing of APP is not amyloidogenic because cleavage takes place within the Aβ region, precluding Aβ generation. The proteolytic processing of APP by ADAM10 produces a secreted ectodomain fragment (sAPPα) that has neuroprotective and neurotrophic properties. For these reasons, increasing ADAM10 activity is viewed as potentially therapeutic for Alzheimer’s disease; however, pharmacological approaches have not yet succeeded.

Besides APP, physiological substrates of ADAM10 include Notch and various immune and growth factor proteins, and the protease itself can be processed into signaling molecules. ADAM10 influences neural development, neuroprotection, and synaptic physiology. Two rare mutations in ADAM10 have been associated with familial late-onset AD.

References

Other Citations

  1. amyloid precursor protein (

Further Reading

News

  1. LOADed ADAM 10 Mutations Bolster Amyloid Hypothesis
  2. Endocytosis Pulls α-Secretase From Synapses
  3. All About ADAM10—The Neuronal α-Secretase
  4. Copper Mountain: Knight Vision—SIRT1 Aids ADAM10, Slays Aβ
  5. More AD Genetics—A Familial Hit from the ADAMs Family
  6. Shedding Assumes α Status

Papers

  1. . Identification and biology of α-secretase. J Neurochem. 2012 Jan;120 Suppl 1:34-45. Epub 2011 Nov 28 PubMed.
  2. . Physiological functions of the amyloid precursor protein secretases ADAM10, BACE1, and Presenilin. Exp Brain Res. 2011 Nov 27; PubMed.
  3. . Regulation of alpha-secretase ADAM10 expression and activity. Exp Brain Res. 2011 Oct 4; PubMed.
  4. . Alpha-secretase cleavage of the amyloid precursor protein: proteolysis regulated by signaling pathways and protein trafficking. Curr Alzheimer Res. 2012 Feb;9(2):165-77. PubMed.
  5. . α-Secretase in Alzheimer's Disease and Beyond: Mechanistic, Regulation and Function in the Shedding of Membrane Proteins. Curr Alzheimer Res. 2011 May 23; PubMed.
  6. . The ADAM metalloproteinases. Mol Aspects Med. 2008 Oct;29(5):258-89. PubMed.