Cathepsin C (CTSC), also known as dipeptidyl peptidase I (DPP1), is a lysosomal cysteine protease that plays crucial roles in protein degradation and activation of serine proteases. It is highly expressed in immune cells and has been implicated in various neurodegenerative diseases through its involvement in neuroinflammation and protein aggregation["@cardona2023"].
Protein Structure and Function
CTSC encodes a cysteine cathepsin that functions as a dipeptidyl peptidase. The enzyme is synthesized as a inactive zymogen and undergoes proteolytic processing to become active. Its primary functions include:
Protein degradation: Catalyzes the removal of dipeptides from the N-terminus of proteins
Protease activation: Activates serine proteases including cathepsin G, elastase, and chymase in hematopoietic cells
Immune function: Plays a role in neutrophil-mediated immune responses[@korkmaz2022]
Role in Neurodegeneration
Alzheimer's Disease
In Alzheimer's disease, CTSC has been linked to [amyloid-beta](/proteins/amyloid-beta) processing and neuroinflammation. Studies have shown elevated CTSC expression in AD brain tissue, particularly in [microglia](/cell-types/microglia-neuroinflammation) surrounding amyloid plaques[@zhao2021]. The enzyme may contribute to:
Modulation of neuroinflammatory responses
Processing of [amyloid precursor protein](/entities/app-protein)
Regulation of [tau](/proteins/tau) phosphorylation
Parkinson's Disease
In Parkinson's disease, CTSC expression is increased in substantia nigra dopaminergic [neurons](/entities/neurons) and in microglia. The enzyme may contribute to:
CTSC levels in cerebrospinal fluid and blood have been investigated as potential biomarkers for:
Disease progression in AD and PD
Treatment response to anti-inflammatory therapies
Interactions and Pathways
Protein Interactions
CTSC interacts with:
Cathepsin G (CTSG): Activation relationship
Elastase (ELANE): Activation relationship
Chymase (CMA1): Activation relationship
A1AT (SERPINA1): Inhibitor
Signaling Pathways
[NF-κB](/entities/nf-kb) signaling pathway
MAPK signaling pathway
Inflammasome activation
Genetic Associations
Polymorphisms
CTSC gene polymorphisms have been associated with:
Inflammatory diseases
Cancer susceptibility
Potential links to neurodegenerative disease risk
Mutations
Rare CTSC mutations cause Papillon-Lefèvre syndrome, characterized by palmoplantar hyperkeratosis and severe periodontitis, but no direct link to neurodegeneration has been established.
Research Directions
Ongoing Studies
CTSC inhibitors for neuroinflammation modulation
CTSC as biomarker for neurodegenerative disease progression
Understanding CTSC-microglia interactions in AD and PD
Key Questions
What is the precise mechanism of CTSC in alpha-synuclein aggregation?
How does CTSC contribute to neuroinflammation in AD?