Caspase-7 Protein

Caspase-7 Protein

Introduction

Caspase-7 is an executioner caspase in the caspase family of cysteine proteases that plays a central role in programmed cell death (apoptosis). It is one of the key effector caspases that executes the apoptotic program by cleaving a broad range of cellular substrates. In neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), caspase-7 activation contributes to neuronal loss through both [apoptosis](/entities/apoptosis) and non-apoptotic functions. Understanding caspase-7's role in neurodegeneration is crucial for developing therapeutic strategies targeting cell death pathways.

Protein Infobox

<div class="infobox infobox-protein"> [@hayward2005]
<div class="infobox-header">Caspase-7 Protein</div> [@burguillos2011]
<div class="infobox-row"><strong>Gene:</strong> [CASP7](/genes/casp7)</div> [@gao2005]
<div class="infobox-row"><strong>UniProt ID:</strong> [P55210](https://www.uniprot.org/uniprot/P55210)</div> [@abraham2002]
<div class="infobox-row"><strong>PDB Structure:</strong> 1F1J, 1I51, 3KAI, 4JJE</div> [@zhang2019]
<div class="infobox-row"><strong>Molecular Weight:</strong> ~35 kDa (pro-caspase), ~20 kDa (active form)</div> [@cote2012]
<div class="infobox-row"><strong>Subcellular Localization:</strong> Cytoplasm, cytoskeleton</div>
<div class="infobox-row"><strong>Protein Family:</strong> Caspase family, peptidase C14 family</div>
</div>

Structure

Caspase-7 is synthesized as a zymogen (pro-caspase-7) that requires activation:

Caspase-7 Protein

Introduction

Caspase-7 is an executioner caspase in the caspase family of cysteine proteases that plays a central role in programmed cell death (apoptosis). It is one of the key effector caspases that executes the apoptotic program by cleaving a broad range of cellular substrates. In neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), caspase-7 activation contributes to neuronal loss through both [apoptosis](/entities/apoptosis) and non-apoptotic functions. Understanding caspase-7's role in neurodegeneration is crucial for developing therapeutic strategies targeting cell death pathways.

Protein Infobox

<div class="infobox infobox-protein"> [@hayward2005]
<div class="infobox-header">Caspase-7 Protein</div> [@burguillos2011]
<div class="infobox-row"><strong>Gene:</strong> [CASP7](/genes/casp7)</div> [@gao2005]
<div class="infobox-row"><strong>UniProt ID:</strong> [P55210](https://www.uniprot.org/uniprot/P55210)</div> [@abraham2002]
<div class="infobox-row"><strong>PDB Structure:</strong> 1F1J, 1I51, 3KAI, 4JJE</div> [@zhang2019]
<div class="infobox-row"><strong>Molecular Weight:</strong> ~35 kDa (pro-caspase), ~20 kDa (active form)</div> [@cote2012]
<div class="infobox-row"><strong>Subcellular Localization:</strong> Cytoplasm, cytoskeleton</div>
<div class="infobox-row"><strong>Protein Family:</strong> Caspase family, peptidase C14 family</div>
</div>

Structure

Caspase-7 is synthesized as a zymogen (pro-caspase-7) that requires activation:

• Pro-domain: Contains a short N-terminal prodomain (~23 amino acids)
• Large subunit (p20): Contains the catalytic cysteine residue
• Small subunit (p12): Completes the active site formation
• Active form: The heterotetrameric active caspase-7 consists of two p20/p12 heterodimers
• Catalytic dyad: His237 and Cys277 form the catalytic dyad essential for protease activity
• Substrate-binding pocket: Recognizes the DEVD tetrapeptide sequence (caspase-7 preferred cleavage site)

Normal Function

In healthy cells, caspase-7 participates in several important processes:

Role in Neurodegeneration

Alzheimer's Disease

Caspase-7 is activated in AD brains and contributes to neuronal death:

• [Amyloid-beta](/proteins/amyloid-beta) toxicity: Aβ exposure triggers caspase-7 activation in [neurons](/entities/neurons)
• Tau cleavage: Caspase-7 cleaves [tau protein](/proteins/tau), generating toxic fragments that may propagate pathology
• Synaptic loss: Caspase-7 activation leads to synaptic protein degradation
• PARP cleavage: Excessive caspase-7 activation causes PARP cleavage, leading to energy depletion and cell death

Parkinson's Disease

In PD, caspase-7 mediates dopaminergic neuron loss:

• Mitochondrial dysfunction: Mitochondrial toxins activate caspase-7
• [Alpha-synuclein](/proteins/alpha-synuclein) toxicity: Caspase-7 is activated by alpha-synuclein aggregates
• Neuroinflammation: Glial activation triggers caspase-7 in neighboring neurons

Amyotrophic Lateral Sclerosis

Caspase-7 contributes to motor neuron degeneration in ALS:

• Mutant SOD1 toxicity: Caspase-7 is activated in ALS models with mutant SOD1
• Excitotoxicity: Glutamate excitotoxicity triggers caspase-7 activation
• Axonal degeneration: Caspase-7 mediates axonal breakdown

Stroke and Traumatic Brain Injury

Caspase-7 activation following ischemia or trauma contributes to secondary neuronal damage.

Therapeutic Targeting

Caspase-7 is a therapeutic target for neurodegenerative diseases:

• Caspase inhibitors: Pan-caspase and caspase-7-selective inhibitors have been developed
• Neuroprotective strategies: Targeting upstream activators to prevent caspase-7 activation
• Peptide-based inhibitors: DEVD-based peptides can block caspase-7 activity
• Challenges: Broad caspase inhibition affects vital cellular functions

Key Publications

See Also

• [CASP7 Gene](/genes/casp7)
• [Caspase-3](/proteins/casp3-protein) - Related executioner caspase
• [Caspase-9](/proteins/casp9-protein) - Initiator caspase in intrinsic apoptosis
• [Apoptosis Pathways](/mechanisms/apoptosis-pathways) - Cellular apoptosis mechanisms
• [Alzheimer's Disease](/diseases/alzheimers-disease) - AD overview
• [Parkinson's Disease](/diseases/parkinsons-disease) - PD overview

External Links

• [UniProt: P55210](https://www.uniprot.org/uniprot/P55210)
• [PDB structures](https://www.rcsb.org/search?q=uniprot:P55210)
• [GeneCards: CASP7](https://www.genecards.org/cgi-bin/carddisp.pl?gene=CASP7)

References