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A Review on Caspases: Key Regulators of Biological Activities and Apoptosis

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Abstract

Caspases are proteolytic enzymes that belong to the cysteine protease family and play a crucial role in homeostasis and programmed cell death. Caspases have been broadly classified by their known roles in apoptosis (caspase-3, caspase-6, caspase-7, caspase-8, and caspase-9 in mammals) and in inflammation (caspase-1, caspase-4, caspase-5, and caspase-12 in humans, and caspase-1, caspase-11, and caspase-12 in mice). Caspases involved in apoptosis have been subclassified by their mechanism of action as either initiator caspases (caspase-8 and caspase-9) or executioner caspases (caspase-3, caspase-6, and caspase-7). Caspases that participate in apoptosis are inhibited by proteins known as inhibitors of apoptosis (IAPs). In addition to apoptosis, caspases play a role in necroptosis, pyroptosis, and autophagy, which are non-apoptotic cell death processes. Dysregulation of caspases features prominently in many human diseases, including cancer, autoimmunity, and neurodegenerative disorders, and increasing evidence shows that altering caspase activity can confer therapeutic benefits. This review covers the different types of caspases, their functions, and their physiological and biological activities and roles in different organisms.

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Data Availability

All data generated or analyzed during this review are included in this review article.

Abbreviations

ALPS:

Autoimmune lymphoproliferative syndrome

AD:

Alzheimer’s disease

ADP-ribose:

Adenosine diphosphate-ribose

ALS:

Amyotrophic lateral sclerosis

APP:

Amyloid beta precursor protein

ARK5:

AMPK-related kinase 5

AMPK:

AMP-Activated protein kinase

APP-C31:

Amyloid beta-protein precursor C-terminal fragments of 31

Ac-YVAD-CMK, AIM-2:

Absent in melanoma 2

AIP-1:

Actin-interacting protein-1

Akt pathway:

Protein kinase B or serine/threonine kinase1

BID:

BH3 interacting-domain death agonist

Bap31 :

B-cell receptor associated protein-31

CED:

Cell death abnormality protein

CED-3:

Cell death abnormality protein-3

CED-4:

Cell death abnormality protein-4

CED-9:

Cell death abnormality protein-9

CEDS:

Caspase eight deficiency stage

CARD:

Caspase recruitment domain

CD95:

Cluster of differentiation 95

CPP-32:

Putative cysteine protease 32

COS:

CV-1 in Origin with SV40 genes (African Green Monkey)

C-JUN-N:

C-JUN N-terminal kinase

Crm A:

Cytokine response modifier A

CNS:

Central nervous system

CCoV-II:

Canine coronavirus-II

CCoV:

Canine coronavirus

CP:

Cyclophosphamide

CASc :

Cascade complex

DNA:

Deoxyribonucleic acid

dATP:

Deoxyadenosine triphosphate

DICA:

2-(2–4-Dichlorophenoxy)-N-(2-mercapto ethyl O acetamide)

D3 :

Vitamin-D/cholecalciferol

DED:

Death effector domain

EAAT2:

Excitatory amino acid transporter-2

EGL-1:

Egg-laying defective protein-1

ER:

Endoplasmic reticulum

ERICE:

Evolutionary related interleukin-1β converting enzyme

Fas:

Fs-7-associated surface antigen

FasL:

Fas- ligand

FICA:

5-Fluro-1H-indole-2 carboxylic acid(2-mercapto-ethyl-amide)

GSDMD:

Gasdermin-D

GSDMD-NT:

Gasdermin-D-N-terminal domain

HCov-OC43:

Human coronavirus OC43

HTT:

Hereditary hemorrhagic telangiectasia

IAP:

Inhibitor of apoptosis

IL-1:

Interleukin-1

ICE:

IL-1 converting enzyme

IFI16:

Interoferon–gamma-inducible protein-1

IRE1α:

Inositol-requiring enzyme/inositol-requiring transmembrane kinase/endoribonuclease 1 alpha

JNK:

C-JUN-N–terminal kinase

JIK:

JNK-inhibitory kinase

LRRs :

Leucine-rich repeats

MC159 :

FLICE inhibitory protein (Mollusccum contagiosum virus)

MAVS:

Mitochondrial antiviral-signaling protein

MEKK1:

Mitogen-activated protein kinase kinase kinase inhibitor1

NLS:

N-terminal nuclear localization signals

NAFLD:

Non-alcoholic fatty liver disease

NUAK:

Member of AMPK (AMP-activated protein kinase)

NOD:

Nucleotide oligomerizatin domain

NLRs :

Nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors

NLRP-3:

NOD-LRR and pyrin domain containg protein-3

NAC:

N-acetyl-L-cysteine

NBA-CARD:

Nijmegan modification of Bethesda assay

NOD2:

Nucleotide-binding oligomerization domain containing protein-2

NRADD:

Neurotrophin receptor alike death domain protein

NF-kB:

Nuclear factor kappa light chain enhancer of activated b-cells

ORF-6:

Accessory protein 6/non-structural protein 6

ORF-3b:

Non-structural protein 3b/accessory protein 3b

Orf-3a:

Non-structural protein 3a/accessory protein 3a

ORF-7a:

Non-structural protein 7a/accessory protein 7a

ORF-4:

Non-structural protein 4/accessory protein 4

PRPA:

Poly-ADP ribose polymerase

PEDE:

Phosphodiesterase

PYD:

Pyrin domain

PARPs :

Poly(ADP-ribose) polymerase inhibitors

PD:

Parkinson’s disease

P21 :

Ras protein/cyclin-dependent kinase inhibitor 1

PRRs :

Pattern recognition receptors

RIG-1:

Retinoic acid-inducible gene 1

RT-PCR:

Reverse transcription polymerase chain reaction

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

siRNA:

Small interfering RNA

sf9:

Clonal isolate of Spodoptera frugiperda sf21 cells

SERPINB1:

Serpin family b member 1

ST14A:

Suppressor of tumorigenicity 14 protein homolog

SARS-CoV:

Severe acute respiratory syndrome-coronavirus

SAT:

Sulfate adenylyl transferase

SARSX4:

SARs coronavirus X4 like protein domain

SADS-CoV:

Swine acute diarrhea syndrome coronavirus

TLR-4:

Toll-like receptor-4

TLR3-TRIF:

Toll-like receptor-3-TRIF

TRIF:

TIR-domain-containing adaptor-inducing interferon-β

TRAF2:

Tumor necrosis factor receptor-associated factor-2

UPR:

Unfolded protein response

UVB:

Ultraviolet

XIAP:

X-linked inhibitor of apoptosis protein YAVD

AFC:

N-Acetyl-Tyr-Val-Ala-Asp-7-Amido-4-trifluro-methylcoumarin

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Acknowledgements

The authors showed thanks to respective institutes that support this review article

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Authors and Affiliations

  1. Department of Zoology, PSSJ College, Banarpal, 759128, Odisha, India

    Gayatri Sahoo

  2. Department of Biotechnology, Academy of Management and Information Technology (AMIT, affiliated to Utkal University), Khurda, 752057, Odisha, India

    Dibyaranjan Samal

  3. Department of Zoology, Mizoram University, Aizawl, 796004, Mizoram, India

    Pratima Khandayataray

  4. Department of Allied Health Sciences, Chitkara School of Health Sciences, Chitkara University, Rajpura, Punjab, 140401, India

    Meesala Krishna Murthy

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  1. Gayatri Sahoo
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  4. Meesala Krishna Murthy
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Contributions

MKM conceived the original idea and designed the outlines of the study. GS and MKM wrote the draft of the manuscript and prepared the figures for the manuscript. GS, DS, PK, and MKM revised and improved the manuscript. All authors have read and approved the final manuscript.

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Correspondence to Meesala Krishna Murthy.

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Sahoo, G., Samal, D., Khandayataray, P. et al. A Review on Caspases: Key Regulators of Biological Activities and Apoptosis. Mol Neurobiol 60, 5805–5837 (2023). https://doi.org/10.1007/s12035-023-03433-5

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