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Lately, researchers realized that a variety of bacterial NOD-like receptors are one of the pattern recognition
and nonbacterial stimuli (e.g. substance related receptors (PRR); they can be assembled into
to autoimmune diseases and cardiovascular and inflammasome under the stimulation of pathogens or
cerebrovascular diseases [7-9] ) can drive programmed other dangerous signals. According to different NLRs,
cell deaths similar to pyroptosis. Meanwhile, in the inflammasome can be classified into four types,
addition to macrophages, there are a variety of cells NLRP-1, 3, 4 Ice Protease-Activating Factor (IPAF),
(such as dendritic cells, etc.) undergoing programmed 5. During pathogen stimulation, effector domains of
death involving caspase-1 activation, thereby different NLRs are exposed to activating caspase-1 through
from caspase-3 mediate apoptosis. Moreover, cells CARD-CARD and PYD-PYD interactions or with
undergoing pyroptosis exhibit a series of cellular the help of ASC directly. Different types of NLRs
changes from complete necrosis to complete the respond to different stimuli. NALP3 is sensible to
apoptosis. [10-12] perforin, extracellular adenosine triphosphate (ATP),
urate crystals, DNA and RNA in virus and ultraviolet.
MECHANISMS OF PYROPTOSIS IPAF is sensible to extracellular pathogens, such as
Pseudomonas, and intracellular pathogens such as
Pyroptosis and caspase-1 are closely associated. Salmonella, Listeria, Shigella, Legionella bacteria.
Caspase family is a group of proteases with high Legionella also needs the help of NALP5-5 to activate
homology, and it can be divided into two categories caspase-1. [16,17] AIM plays an important role in viral
according to its relationship with apoptosis and infections; its function is to identify DNA cytoplasm. It
pyroptosis. One includes apoptosis-related proteases, is a cytoplasmic DNA transducer, one of PRRs sensible
for instance caspase-3, the executor of apoptosis, and to extrinsic DNA. It belongs to HIN-200 family, with
also caspase-2, 6, 7, 8, 9, 10 etc. Caspase-3 is activated a PYD domain in amino-terminal and an HIN-200
by co-action of caspase-2, 6, 7, 8, 9, 10 etc., and activated domain in carboxy-terminal. [18] In virus-infected cells,
caspase-3 could induce DNA dissolution, proteolysis, AIM2 and caspase-1 can form inflammasome to induce
and downstream events leading to apoptosis. The innate immunity and resist intracellular bacteria and
second is inflammation-associated proteases, including DNA viruses. [19] RIG-I also binds to the adaptor ASC to
caspase-1 and caspase-4, 5, 11, 12, 13, 14 etc., taking trigger caspase-1-dependent inflammasome activation
part in cytokines-mediated inflammatory response. [13] by a mechanism independent from CARD and NLRP3
Caspase-1 is not involved in apoptosis, but represents in RNA infection. [15] The effects of ASC are to combine
the key factor in pyrotosis. Caspase-1 is an IL-1β caspase-1 and NLRP1, NLRP3, AIM2, RIG-I together.
converting enzyme. Pro-caspase-1 does not have The mechanism is mediated by the PYD domain in the
biological activity when produced. Its molecular weight carboxyl terminus of ASC combined with PYD domain
is 45 kDa, constituted by the three domains, including in NLRP1 NLRP3 and AIM, with the CARD domain
the caspase activation and recruitment domains (CARD) in N-terminal of ASC combined with pro-caspase-1’s
structure in NH -terminal, a large subunit about 20 kDa, CARD domain. In addition, ASC can be assembled into
2
and a small subunit about 10 kDa. Then, pro-caspase-1 ASC dimer without the participation of NLRs, and ASC
is converted into heterodimer in the cytoplasm, and dimer can activate caspase-1 directly. This ASC dimer
further assembled into biologically active tetrameric has been named Pyroptosome recently. [20]
caspase-1. [13] This activation process is regulated by
a multi-protein complex in the cytoplasm named The activators of the inflammasomes can be divided into
inflammasome. [14] two categories: pathogen associated molecular patterns
activate a host-defense reaction, and damage associated
Inflammasome is a multi-protein complex composed molecular patterns activate a self-defense mechanism in
by NOD-like receptors (NLRs), proteins containing response to danger signals. Activators include bacteria,
[21]
NATCH, leucine-rich repeat and PYD domains (NLRP1 virus, fungus, protozoa, microbial proteins, crystalline
NLRC4 NLRP3 NAIP5 and NLRC5), or absent in urea, RNA, Alum, ATP, potassium efflux, fatty acids, Aβ,
melanoma 2 (AIM2), or Caspase-1 etc. Some of the and most recently, degraded mitochondrial DNA. [22-24]
inflammasomes also contain apoptosis-associated Overall the assembly and activation of inflammasomes
speck-like proteins containing CARD (ASC). Recent are cell-type and stimulus-specific. [25,26]
studies have confirmed that retinoic acid-inducible
gene I (RIG-I), one of the receptors of some RNA With inflammasome, pro-caspase-1 is activated to
viruses, can form inflammasome with ASC, without caspase-1. Its function includes conversion of the pro-IL-
the participation of NLRs. [15] Under the regulation of 1β and pro-IL-18 into active IL-1β and IL-18. When bound
inflammasome, pro-caspase-1 is activated, promoting to their receptors, IL-1R and IL-18R, they lead to nuclear
the processing and maturation of pro-inflammatory factor-κB dependent gene transcription. [27,28] IL-1β is a
factors such as IL-1 and IL-18. key molecule in inflammasome initiation and IL-18 can

Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014 61