Caspases in apoptotic death

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Caspases are the central mediators of normal and pathological apoptotic death. They are cysteine proteases that cleave after aspartic acid. The inactive pro-enzymes are proteolytically processed and activated through mechanisms of recruitment to signalling complexes, upstream activator caspases or autoactivation. Many amplifying cascades exist in caspase activation pathways that are evolutionarily conserved. The human caspase family contains at least 10 members which form 3 groups based on substrate specificity, proteolytic and functional actions. The crystal structure has been solved for members from two of these groups with inhibitory peptides bound in the active site. These structures have allowed tremendous insight into mechanisms of catalysis, substrate binding and substrate specificity. Enlightened knowledge of enzyme-substrate interactions has led to the design of many inhibitors that are active in animal models of caspase-mediated cell death. Testing in animal models should lead to drugs for therapeutic intervention in the many human diseases characterised by excessive apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)37-50
Number of pages14
JournalExpert Opinion on Investigational Drugs
Volume8
Issue number1
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Caspases
Substrate Specificity
Cell Death
Animal Models
Cysteine Proteases
Enzymes
Catalysis
Aspartic Acid
Catalytic Domain
Peptides
Pharmaceutical Preparations
Therapeutics

Keywords

  • Alzheimer's disease
  • Arthritis
  • Atherosclerosis
  • Autommunity
  • Bone disease
  • Cardiovascular
  • Diabetes
  • Inflammation
  • Ischaemia
  • Multiple sclerosis
  • Neoplasm
  • Neurodegeneration
  • Parkinson's disease
  • Sepsis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Caspases in apoptotic death. / Denner, Larry.

In: Expert Opinion on Investigational Drugs, Vol. 8, No. 1, 1999, p. 37-50.

Research output: Contribution to journalArticle

@article{7e1d78e25f194f9583862755e07e7290,
title = "Caspases in apoptotic death",
abstract = "Caspases are the central mediators of normal and pathological apoptotic death. They are cysteine proteases that cleave after aspartic acid. The inactive pro-enzymes are proteolytically processed and activated through mechanisms of recruitment to signalling complexes, upstream activator caspases or autoactivation. Many amplifying cascades exist in caspase activation pathways that are evolutionarily conserved. The human caspase family contains at least 10 members which form 3 groups based on substrate specificity, proteolytic and functional actions. The crystal structure has been solved for members from two of these groups with inhibitory peptides bound in the active site. These structures have allowed tremendous insight into mechanisms of catalysis, substrate binding and substrate specificity. Enlightened knowledge of enzyme-substrate interactions has led to the design of many inhibitors that are active in animal models of caspase-mediated cell death. Testing in animal models should lead to drugs for therapeutic intervention in the many human diseases characterised by excessive apoptotic cell death.",
keywords = "Alzheimer's disease, Arthritis, Atherosclerosis, Autommunity, Bone disease, Cardiovascular, Diabetes, Inflammation, Ischaemia, Multiple sclerosis, Neoplasm, Neurodegeneration, Parkinson's disease, Sepsis",
author = "Larry Denner",
year = "1999",
doi = "10.1517/13543784.8.1.37",
language = "English (US)",
volume = "8",
pages = "37--50",
journal = "Expert Opinion on Investigational Drugs",
issn = "1354-3784",
publisher = "Taylor and Francis Ltd.",
number = "1",

}

TY - JOUR

T1 - Caspases in apoptotic death

AU - Denner, Larry

PY - 1999

Y1 - 1999

N2 - Caspases are the central mediators of normal and pathological apoptotic death. They are cysteine proteases that cleave after aspartic acid. The inactive pro-enzymes are proteolytically processed and activated through mechanisms of recruitment to signalling complexes, upstream activator caspases or autoactivation. Many amplifying cascades exist in caspase activation pathways that are evolutionarily conserved. The human caspase family contains at least 10 members which form 3 groups based on substrate specificity, proteolytic and functional actions. The crystal structure has been solved for members from two of these groups with inhibitory peptides bound in the active site. These structures have allowed tremendous insight into mechanisms of catalysis, substrate binding and substrate specificity. Enlightened knowledge of enzyme-substrate interactions has led to the design of many inhibitors that are active in animal models of caspase-mediated cell death. Testing in animal models should lead to drugs for therapeutic intervention in the many human diseases characterised by excessive apoptotic cell death.

AB - Caspases are the central mediators of normal and pathological apoptotic death. They are cysteine proteases that cleave after aspartic acid. The inactive pro-enzymes are proteolytically processed and activated through mechanisms of recruitment to signalling complexes, upstream activator caspases or autoactivation. Many amplifying cascades exist in caspase activation pathways that are evolutionarily conserved. The human caspase family contains at least 10 members which form 3 groups based on substrate specificity, proteolytic and functional actions. The crystal structure has been solved for members from two of these groups with inhibitory peptides bound in the active site. These structures have allowed tremendous insight into mechanisms of catalysis, substrate binding and substrate specificity. Enlightened knowledge of enzyme-substrate interactions has led to the design of many inhibitors that are active in animal models of caspase-mediated cell death. Testing in animal models should lead to drugs for therapeutic intervention in the many human diseases characterised by excessive apoptotic cell death.

KW - Alzheimer's disease

KW - Arthritis

KW - Atherosclerosis

KW - Autommunity

KW - Bone disease

KW - Cardiovascular

KW - Diabetes

KW - Inflammation

KW - Ischaemia

KW - Multiple sclerosis

KW - Neoplasm

KW - Neurodegeneration

KW - Parkinson's disease

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=0032945917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032945917&partnerID=8YFLogxK

U2 - 10.1517/13543784.8.1.37

DO - 10.1517/13543784.8.1.37

M3 - Article

C2 - 15992057

AN - SCOPUS:0032945917

VL - 8

SP - 37

EP - 50

JO - Expert Opinion on Investigational Drugs

JF - Expert Opinion on Investigational Drugs

SN - 1354-3784

IS - 1

ER -