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Pyroptosis in neurodegenerative diseases: from bench to bedside

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Abstract

The central nervous system regulates all aspects of physiology to some extent. Neurodegenerative diseases (NDDs) lead to the progressive loss and dysfunction of neurons, which are particularly evident in Alzheimer’s disease, Parkinson’s disease, and many other conditions. NDDs are multifactorial diseases with complex pathogeneses, and there has been a rapid increase in the prevalence of NDDs. However, none of these diseases can be cured, making the development of novel treatment strategies an urgent necessity. Numerous studies have indicated how pyroptosis induces inflammation and affects many aspects of NDD. Therefore, components related to pyroptosis are potential therapeutic candidates and are attracting increasing attention. Here, we review the role of pyroptosis in the pathogenesis of NDDs and potential treatment options. Additionally, several of the current drugs and relevant inhibitors are discussed. Through this article, we provide theoretical support for exploring new therapeutic targets and updating clinical treatment strategies for NDDs. Notably, pyroptosis, a recently widely studied mode of cell death, is still under-researched compared to other traditional forms of cell death. Moreover, the focus of research has been on the onset and progression of NDDs, and the lack of organ-specific target discovery and drug development is a common problem for many basic studies. This urgent problem requires scientists and companies worldwide to collaborate in order to develop more effective drugs against NDDs.

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Data availability

Data sharing is not applicable to this article. We also used data from https://platform.opentargets.org/.

Abbreviations

CNS:

central nervous system

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

NDDs:

neurodegenerative diseases

PNS:

peripheral nervous system

SCI:

spinal cord injury

ES:

epilepsy

ALS:

amyotrophic lateral sclerosis

HD:

Huntington’s disease

MS:

multiple sclerosis

CED-3:

cell death mutant 3

GSDM:

gasdermin

LPS:

lipopolysaccharide

IL:

interleukin

PRRs:

pattern recognition receptors

PAMPs:

pathogen-associated molecular patterns

DAMPs:

damage-associated molecular patterns

NLRs:

NOD-like receptors

NLRC4:

NLR family CARD domain-containing 4

NLRP3:

NOD-like receptor protein 3

NLRP6:

NOD-like receptor protein 6

CARD/ASC:

caspase recruitment domain

AIM2:

absent in melanoma 2

LRR:

leucine-rich repeat

PYD:

pyrin domain

GSDMD:

gasdermin D

FDA:

Food and Drug Administration

Aβ:

amyloid-β

MCNs:

mouse cortical neurons

NFTs:

neurofibrillary tangles

LiCl:

lithium chloride

FSK:

forskolin

TXNIP:

thioredoxin-interacting protein

ER:

endoplasmic reticulum

FTD:

frontotemporal dementia

αSyn:

α-synuclein

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

L-DOPA:

levodopa

ATP:

adenosine triphosphate

mHTT:

mutant huntingtin

Gal-3:

galectin-3

PMS:

progressive MS

PPMS:

relapsing-remitting MS

SPMS:

secondary progressive MS

ODCs:

oligodendrocytes

TNF-α:

tumor necrosis factor-α

EAE:

experimental autoimmune encephalomyelitis

ROS:

reactive oxygen species

JOA:

Japanese Orthopaedic Association

NDI:

neck disability index

CD73:

ecto-5′-nucleotidase

GFAP:

glial fibrillary acidic protein

MOG:

myelin oligodendrocyte glycoprotein

mRNA:

messenger ribonucleic acid

ADK:

adenosine kinase

KA:

kainic acid

TwFI:

Tripterygium wilfordii Hook F

IHC:

immunohistochemistry

miRNA:

microRNA

MSC:

mesenchymal stem cell

ADMSC:

adipose-derived MSC

Exo:

exosomal

LID:

levodopa-induced dyskinesia

Sal:

salidroside

PARP-1:

poly-(ADP-ribose) polymerase 1

NIIs:

neuronal intranuclear inclusions

DMF:

dimethyl fumarate

Cys:

cysteine

LDH:

lactate dehydrogenase

MMF:

2-monomethyl fumarate

GSDMD-N:

GSDMD-N-terminal domain

NT5E:

ecto-5′-nucleotidase

ASMs:

antiseizure medications

CLMD:

Chaihu-Longgu-Muli decoction

TCM:

traditional Chinese medicine

TLE:

temporal lobe epilepsy

CAPS:

cryopyrin-associated periodic syndrome

TYK2:

tyrosine kinase 2

WDL:

wedelolactone

IKK:

IκB kinase

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Acknowledgements

We would like to thank all the authors for their work and dedication.

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Funding

Partial financial support was received from the National Natural Science Foundation of China (No. 82101337) and a BSKY Scientific Research Grant from Anhui Medical University (XJ201813).

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Authors and Affiliations

  1. College of Life Sciences, Anhui Medical University, Tanghe Road, Hefei, 230012, Anhui, People’s Republic of China

    Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou & Rui-jie Zhang

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  1. Ke-jia Wu
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  2. Wan-rong Wang
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  3. Qian-hui Cheng
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  4. Hao Li
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  7. Rui-jie Zhang
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Contributions

Conceptualization: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; methodology: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; formal analysis and investigation: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; writing—original draft preparation: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; writing—review and editing: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; funding acquisition: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; resources: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang; supervision: Ke-jia Wu, Wan-rong Wang, Qian-hui Cheng, Hao Li, Wei-zhen Yan, Fei-ran Zhou, Rui-jie Zhang

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Correspondence to Rui-jie Zhang.

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Wu, Kj., Wang, Wr., Cheng, Qh. et al. Pyroptosis in neurodegenerative diseases: from bench to bedside. Cell Biol Toxicol 39, 2467–2499 (2023). https://doi.org/10.1007/s10565-023-09820-x

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