congenital neuronal ceroid lipofuscinosis At least four mutations in the CTSD gene have been found to cause congenital neuronal ceroid lipofuscinosis (NCL). Congenital NCL is characterized by muscle rigidity, respiratory failure, severe seizures, and death in infancy. The CTSD gene mutations that cause congenital NCL lead to a complete lack of cathepsin D enzyme activity. As a result, proteins and other materials are not broken down properly. In the lysosomes, these substances accumulate into fatty substances called lipopigments. These accumulations occur in cells throughout the body, but neurons are likely particularly vulnerable to damage caused by the abnormal cell materials and the loss of cathepsin D function. Early and widespread cell death in congenital NCL leads to severe signs and symptoms and death in infancy.

     The CTSD gene provides instructions for making an enzyme called cathepsin D. Cathepsin D is one of a family of cathepsin proteins that act as proteases, which modify proteins by cutting them apart. Cathepsin D is found in many types of cells and is active in lysosomes, which are compartments within cells that digest and recycle different types of molecules. By cutting proteins apart, cathepsin D can break proteins down, turn on (activate) proteins, and regulate self-destruction of the cell (apoptosis). Cathepsin D is produced as an inactive enzyme, called a preproenzyme, which has extra protein segments attached. These segments must be removed, followed by additional processing steps, for the enzyme to become active.

The following transcription factors affect gene expression:

• PPAR-gamma1
• p53
• Egr-1
• AP-1
• c-Jun
• c-Fos
• STAT1
• STAT1beta
• STAT1alpha

Tissue specificity:

Expressed in the aorta extrcellular space (at protein level).

Molecular Function:

• Aspartic-Type Endopeptidase Activity
• Cysteine-Type Endopeptidase Activity
• Serine-Type Endopeptidase Activity

Biological Processes:

• Autophagy
• Antigen Processing And Presentation Of Exogenous Peptide Antigen Via Mhc Class Ii
• Protein Catabolic Process
• Collagen Catabolic Process

Drug Bank:

• Insulin Regular