TRIF

Tripeptidyl peptidase 1 (TPP1) is an enzyme that in humans is encoded by the TPP1 gene. TPP1 is a lysosomal serine protease that plays a crucial role in the degradation of proteins by cleaving tripeptides from the N-terminus of polypeptides. This enzyme is particularly important in the context of neuronal ceroid lipofuscinoses (NCLs), a group of neurodegenerative disorders.

Function

TPP1 is involved in the breakdown of proteins within the lysosome, a cellular organelle responsible for degrading and recycling cellular waste. The enzyme specifically removes tripeptides from the N-terminus of proteins, a process essential for the proper turnover and recycling of proteins within the cell. This activity is critical for maintaining cellular homeostasis and preventing the accumulation of undegraded proteins, which can be toxic to cells.

Clinical Significance

Mutations in the TPP1 gene are associated with a form of neuronal ceroid lipofuscinosis known as CLN2 disease, or late-infantile Batten disease. This condition is characterized by the accumulation of lipofuscin, a lipid-containing pigment, in the body's tissues, leading to progressive neurodegeneration. Symptoms typically begin in early childhood and include seizures, vision loss, and motor and cognitive decline.

Genetics

The TPP1 gene is located on chromosome 11 at the p15.4 region. It consists of multiple exons and encodes a protein that is initially synthesized as an inactive precursor. This precursor undergoes proteolytic processing to become an active enzyme within the lysosome.

Structure

TPP1 is a serine protease, which means it uses a serine residue in its active site to cleave peptide bonds. The enzyme is synthesized as a preproenzyme and undergoes several processing steps to become active. The mature enzyme is a homodimer, meaning it consists of two identical subunits.

Research and Therapeutic Approaches

Research into TPP1 has focused on understanding its role in neurodegenerative diseases and developing therapies to treat conditions like CLN2 disease. Enzyme replacement therapy (ERT) and gene therapy are two approaches being explored to restore TPP1 function in affected individuals. Clinical trials are ongoing to evaluate the safety and efficacy of these treatments.

Also see

• Neuronal ceroid lipofuscinoses
• Lysosome
• Protease
• Gene therapy