Death-Associated Protein Kinase 1 as a Promising Drug Target in Cancer and Alzheimer's Disease.
Alzheimer's Disease (AD)
Death-Associated Protein Kinase 1 (DAPK1)
apoptosis
cancer
kinase modulator
phosphorylation
therapeutic target.
Journal
Recent patents on anti-cancer drug discovery
ISSN: 2212-3970
Titre abrégé: Recent Pat Anticancer Drug Discov
Pays: United Arab Emirates
ID NLM: 101266081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
10
10
2018
revised:
23
11
2018
accepted:
13
12
2018
pubmed:
21
12
2018
medline:
12
2
2020
entrez:
21
12
2018
Statut:
ppublish
Résumé
Death-Associated Protein Kinase 1 (DAPK1) plays an important role in apoptosis, tumor suppression and neurodegeneration including Alzheimer's Disease (AD). This review will describe the diverse roles of DAPK1 in the development of cancer and AD, and the current status of drug development targeting DAPK1-based therapies. Reports of DAPK1 regulation, function and substrates were analyzed using genetic DAPK1 manipulation and chemical DAPK1 modulators. DAPK1 expression and activity are deregulated in cancer and AD. It is down-regulated and/or inactivated by multiple mechanisms in many human cancers, and elicits a protective effect to counteract numerous death stimuli in cancer, including activation of the master regulator Pin1. Moreover, loss of DAPK1 expression has correlated strongly with tumor recurrence and metastasis, suggesting that lack of sufficient functional DAPK1 might contribute to cancer. In contrast, DAPK1 is highly expressed in the brains of most human AD patients and has been identified as one of the genetic factors affecting susceptibility to late-onset AD. The absence of DAPK1 promotes efficient learning and better memory in mice and prevents the development of AD by acting on many key proteins including Pin1 and its downstream targets tau and APP. Recent patents show that DAPK1 modulation might be used to treat both cancer and AD. DAPK1 plays a critical role in diverse physiological processes and importantly, its deregulation is implicated in the pathogenesis of either cancer or AD. Therefore, manipulating DAPK1 activity and/or expression may be a promising therapeutic option for cancer or AD.
Sections du résumé
BACKGROUND
BACKGROUND
Death-Associated Protein Kinase 1 (DAPK1) plays an important role in apoptosis, tumor suppression and neurodegeneration including Alzheimer's Disease (AD).
OBJECTIVE
OBJECTIVE
This review will describe the diverse roles of DAPK1 in the development of cancer and AD, and the current status of drug development targeting DAPK1-based therapies.
METHODS
METHODS
Reports of DAPK1 regulation, function and substrates were analyzed using genetic DAPK1 manipulation and chemical DAPK1 modulators.
RESULTS
RESULTS
DAPK1 expression and activity are deregulated in cancer and AD. It is down-regulated and/or inactivated by multiple mechanisms in many human cancers, and elicits a protective effect to counteract numerous death stimuli in cancer, including activation of the master regulator Pin1. Moreover, loss of DAPK1 expression has correlated strongly with tumor recurrence and metastasis, suggesting that lack of sufficient functional DAPK1 might contribute to cancer. In contrast, DAPK1 is highly expressed in the brains of most human AD patients and has been identified as one of the genetic factors affecting susceptibility to late-onset AD. The absence of DAPK1 promotes efficient learning and better memory in mice and prevents the development of AD by acting on many key proteins including Pin1 and its downstream targets tau and APP. Recent patents show that DAPK1 modulation might be used to treat both cancer and AD.
CONCLUSION
CONCLUSIONS
DAPK1 plays a critical role in diverse physiological processes and importantly, its deregulation is implicated in the pathogenesis of either cancer or AD. Therefore, manipulating DAPK1 activity and/or expression may be a promising therapeutic option for cancer or AD.
Identifiants
pubmed: 30569876
pii: PRA-EPUB-95304
doi: 10.2174/1574892814666181218170257
pmc: PMC6751350
doi:
Substances chimiques
DAPK1 protein, human
EC 2.7.11.1
Death-Associated Protein Kinases
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
144-157Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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