Autophagy and Apoptosis Specific Knowledgebases-guided Systems Pharmacology Drug Research

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BACKGROUND: Autophagy and apoptosis are the basic physiological processes in cells that clean up aged and mutant cellular components or even the entire cells. Both autophagy and apoptosis are disrupted in most major diseases such as cancer and neurological disorders. Recently, increasing attention has been paid to understand the crosstalk between autophagy and apoptosis due to their tightly synergetic or opposite functions in several pathological processes.

OBJECTIVE: This study aims to assist autophagy and apoptosis-related drug research, clarify the intense and complicated connections between two processes, and provide a guide for novel drug development.

METHODS: We established two chemical-genomic databases which are specifically designed for autophagy and apoptosis, including autophagy- and apoptosis-related proteins, pathways and compounds. We then performed network analysis on the apoptosis- and autophagy-related proteins and investigated the full protein-protein interaction (PPI) network of these two closely connected processes for the first time.

RESULTS: The overlapping targets we discovered show a more intense connection with each other than other targets in the full network, indicating a better efficacy potential for drug modulation. We also found that Death-associated protein kinase 1 (DAPK1) is a critical point linking autophagy- and apoptosis-related pathways beyond the overlapping part, and this finding may reveal some delicate signaling mechanism of the process. Finally, we demonstrated how to utilize our integrated computational chemogenomics tools on in silico target identification for small molecules capable of modulating autophagy- and apoptosis-related pathways.

CONCLUSION: The knowledge-bases for apoptosis and autophagy and the integrated tools will accelerate our work in autophagy and apoptosis-related research and can be useful sources for information searching, target prediction, and new chemical discovery.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Current cancer drug targets - 19(2019), 9 vom: 22., Seite 716-728

Sprache:

Englisch

Beteiligte Personen:

Fan, Peihao [VerfasserIn]
Wang, Nanyi [VerfasserIn]
Wang, Lirong [VerfasserIn]
Xie X-Q [VerfasserIn]

Links:

Volltext

Themen:

Antineoplastic Agents
Apoptosis
Autophagy
Cancer
Journal Article
Network analysis
Neurological diseases
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Systems pharmacology.

Anmerkungen:

Date Completed 21.09.2020

Date Revised 21.09.2020

published: Print

Citation Status MEDLINE

doi:

10.2174/1568009619666190206122149

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM293539944