Functions of 'A disintegrin and metalloproteases (ADAMs)' in the mammalian nervous system.
ADAM
Ectodomain shedding
Metalloprotease
Neural development
Neurological disease
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
22
05
2019
accepted:
29
05
2019
revised:
22
05
2019
pubmed:
27
6
2019
medline:
30
7
2019
entrez:
26
6
2019
Statut:
ppublish
Résumé
'A disintegrin and metalloproteases' (ADAMs) are a family of transmembrane proteins with diverse functions in multicellular organisms. About half of the ADAMs are active metalloproteases and cleave numerous cell surface proteins, including growth factors, receptors, cytokines and cell adhesion proteins. The other ADAMs have no catalytic activity and function as adhesion proteins or receptors. Some ADAMs are ubiquitously expressed, others are expressed tissue specifically. This review highlights functions of ADAMs in the mammalian nervous system, including their links to diseases. The non-proteolytic ADAM11, ADAM22 and ADAM23 have key functions in neural development, myelination and synaptic transmission and are linked to epilepsy. Among the proteolytic ADAMs, ADAM10 is the best characterized one due to its substrates Notch and amyloid precursor protein, where cleavage is required for nervous system development or linked to Alzheimer's disease (AD), respectively. Recent work demonstrates that ADAM10 has additional substrates and functions in the nervous system and its substrate selectivity may be regulated by tetraspanins. New roles for other proteolytic ADAMs in the nervous system are also emerging. For example, ADAM8 and ADAM17 are involved in neuroinflammation. ADAM17 additionally regulates neurite outgrowth and myelination and its activity is controlled by iRhoms. ADAM19 and ADAM21 function in regenerative processes upon neuronal injury. Several ADAMs, including ADAM9, ADAM10, ADAM15 and ADAM30, are potential drug targets for AD. Taken together, this review summarizes recent progress concerning substrates and functions of ADAMs in the nervous system and their use as drug targets for neurological and psychiatric diseases.
Identifiants
pubmed: 31236626
doi: 10.1007/s00018-019-03173-7
pii: 10.1007/s00018-019-03173-7
doi:
Substances chimiques
Potassium Channels
0
ADAM Proteins
EC 3.4.24.-
Types de publication
Journal Article
Review
Langues
eng
Pagination
3055-3081Références
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