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Review Article

Pyroptosis and neurological diseases

Zhen Xie , Gang Zhao 1
1,2
1 Department of Neurology, Xijing Hospital, Forth Military Medical University, Xi’an 710032, Shaanxi, China
2 Department of Neurology, Shaanxi Provincial People’s Hospital, Xi’an 710068, Shaanxi, China

ABSTRA CT
Pyroptosis is a new process of programmed cell death, which has been discovered and confirmed in recent years. Its cardinal features
include activation of caspase‑1 and a massive release of inflammatory cytokines (interleukin (IL)‑1β, IL‑18), etc. The morphological
characteristics, occurrence and regulatory mechanisms of the pyroptosis greatly, differ from other cell death mechanisms such as
apoptosis and necrosis. It has already been proven that pyroptosis participates and plays an important role in a wide range of neuronal
diseases. Here, we review the current understanding of the pyroptosis and its roles in neurological diseases.

Key words: Caspase-1, inflammasome, interleukin-1β, interleukin‑18, neurological diseases, pyroptosis

INTRODUCTION Pyroptosis was first observed in 1992 when Zychlinsky
et al. described that Shigella flexneri can induce
Cell death is a critical and inevitable phase common programmed cell death in macrophage, but this process
to all cell types. A deeper understanding of cell death was mediated by a caspase-1, and the iconic molecule
in its form and nature is critical to shed new light in apoptosis, caspase-3, was not apparently involved.
on the emergence, development and treatment of This observation suggested that such programmed
diseases. Many different types of cell death patterns cell death was different from apoptosis. Subsequent
[1]
have been discovered in the last years; among that studies confirmed that in S. flexneri specific caspase-1
pyroptosis is one of the most recent. It is now widely blocker Ac-YVAD-CHO inhibited programmed cell death
accepted that this mechanism contributes to the of macrophages, whereas caspase-1 knockout could
development of neurological diseases. In this review, protect macrophages from death following S. flexneri
we first describe the definition of the pyroptosis and its infection. [1,2] In contrast, caspase-3 specific blockers
basic mechanisms and discuss how pyroptosis and its and caspase-3 knockout macrophages did not show any
relevant molecules participate in neurological diseases effects. Then, in 2001, Cookson and Brennan found a
[3]
and their progression. type of caspase-1 dependent cell death in Salmonella
infected macrophages, and for the first time named it
THE HISTORY OF PYROPTOSIS AND ITS “pyroptosis”, its meaning deriving from the Greek root
CHARACTERISTICS pyro (fireworks) and ptosis (to-sis) (death). [4]

The understanding of cell death has changed a lot In the process of the pyroptosis, activated caspase-1
through decades. Nowadays we believe that cell death mediates massive generation of pro-inflammatory
[5]
can be roughly divided into necrosis and programmed cytokines, interleukin (IL)-1β, IL-18, leading to
cell death, the latter one, including apoptosis, oncosis, cell morphological changes similar to apoptosis,
autophagy, etc., as well as pyroptosis that will be such as nucleus pycnosis, DNA fragmentation and
discussed in this review. TUNEL staining positivity, etc. However, in contrast
to apoptosis, in pyroptotic cell, the integrity of the
Access this article online cell membrane is not preserved and micro-pores with
Quick Response Code: diameter about 1-2 nm are formed on it, resulting in
Website: potassium efflux, intracellular and extracellular ion
www.nnjournal.net
imbalance, cell swelling and rupture. Meanwhile,
DOI: the pro-inflammatory cytokines and cytoplasmic
10.4103/2347-8659.139716 components are released to the extracellular space,
causing focal inflammation and cell death. [6]

Corresponding Author: Prof. Gang Zhao, Department of Neurology, Xijing Hospital, Fourth Military Medical University,
No. 169 Changle West Road, Xi’an 710032, Shaanxi, China. E‑mail: xiezhenhh@163.com

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