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Review
. 2018 May;51(5):219-224.
doi: 10.5483/bmbrep.2018.51.5.074.

The role of necroptosis in the treatment of diseases

Young Sik Cho  1
Affiliations
Review

The role of necroptosis in the treatment of diseases

Young Sik Cho. BMB Rep. 2018 May.

Abstract

Necroptosis is an emerging form of programmed cell death occurring via active and well-regulated necrosis, distinct from apoptosis morphologically, and biochemically. Necroptosis is mainly unmasked when apoptosis is compromised in response to tumor necrosis factor alpha. Unlike apoptotic cells, which are cleared by macrophages or neighboring cells, necrotic cells release danger signals, triggering inflammation, and exacerbating tissue damage. Evidence increasingly suggests that programmed necrosis is not only associated with pathophysiology of disease, but also induces innate immune response to viral infection. Therefore, necroptotic cell death plays both physiological and pathological roles. Physiologically, necroptosis induce an innate immune response as well as premature assembly of viral particles in cells infected with virus that abrogates host apoptotic machinery. On the other hand, necroptosis per se is detrimental, causing various diseases such as sepsis, neurodegenerative diseases and ischemic reperfusion injury. This review discusses the signaling pathways leading to necroptosis, associated necroptotic proteins with target-specific inhibitors and diseases involved. Several studies currently focus on protective approaches to inhibiting necroptotic cell death. In cancer biology, however, anticancer drug resistance severely hampers the efficacy of chemotherapy based on apoptosis. Pharmacological switch of cell death finds therapeutic application in drug- resistant cancers. Therefore, the possible clinical role of necroptosis in cancer control will be discussed in brief. [BMB Reports 2018; 51(5): 219-224].

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Conflict of interest statement

CONFLICTS OF INTEREST

The authors have no conflicting interests.

Figures

Fig. 1
Fig. 1
Necroptosis regulators and signaling pathways in necroptosis activation. Upon TNF receptor ligation, a signal transduction mediated via RIP1, caspase activation, and tBID cleavage occurs, resulting in apoptotic cell death. Active caspase-8 inhibits necroptosis via cleavage of RIP1 and RIP3. Inhibition of caspase leads to the formation of a physical complex of RIP1 with RIP3 to trigger downstream signaling events including MLKL and PGAM5 recruitment, and transduction of cytosolic death signals to mitochondria, resulting in necroptosis.
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