RESEARCH: PARKINSONS
FOLDING PROJECT #18501 PROFILE

Two projects study Transmembrane Protein 175 (TMEM175), a channel that moves potassium ions in cells. Project 18500 studies normal TMEM175, linked to Parkinson's disease. Project 18501 changes a part of the protein and tests if it helps TMEM175 switch between open and closed states. Understanding TMEM175 could lead to new Parkinson's treatments.

Project 18500 is running wild-type Transmembrane Protein 175 (TMEM175).

Transmembrane Protein 175 (TMEM175) is a protein in the lysosomal membrane that functions as a "channel" for potassium ions to move between the open space in the cell (the cytoplasm) and the space within the lysosome (the lysosomal lumen).

TMEM175 is thought to play an important role in autophagy as a lysosomal protein, but its exact function in this process is not yet clear.

Nevertheless, dysfunction of TMEM175 is implicated in the development of Parkinson’s.

We know this because several mutational variants of TMEM175 have been identified in Parkinson’s patients, and experiments have shown that mice with these variants have some of the molecular and behavioral hallmarks of Parkinson’s.

An understanding of the fundamental mechanisms of TMEM175 will lead to new ways to discover drugs or therapeutic interventions to treat, prevent, or potentially even reverse Parkinson’s Disease. Project 18501 is the same as 18500 except that a histidine in the pore is modelled as neutral instead of positively charged (i.e.

it has one less proton).

We are testing to see if we need this as a way to bridge the open and closed states of the channel.

Transmembrane Protein 175

A protein found in lysosomal membranes that acts as a potassium ion channel.

Transmembrane Protein 175 (TMEM175) is a vital component of lysosomes, the cell's recycling centers. It allows potassium ions to pass through the lysosomal membrane, playing a role in cellular processes like autophagy. Dysfunction of TMEM175 is linked to Parkinson's disease, highlighting its significance in neurological health.

Lysosome

A membrane-bound organelle within cells responsible for breaking down waste materials and cellular debris.

Lysosomes are like the cell's recycling centers. They contain powerful enzymes that break down worn-out organelles, proteins, and other cellular waste. This process is essential for maintaining cellular health and removing harmful substances.

Autophagy

A process by which cells degrade and recycle their own components.

Autophagy is a natural cellular process where cells break down and reuse their own parts. This helps maintain cellular health, remove damaged components, and provide energy during times of stress.

Parkinson's Disease

A progressive neurodegenerative disorder affecting movement.

Parkinson's disease is a debilitating brain disorder that causes tremors, stiffness, slow movements, and balance problems. It results from the loss of dopamine-producing nerve cells in a part of the brain called the substantia nigra.

Mutation

A permanent change in the DNA sequence.

Mutations are alterations in the genetic code (DNA). They can be caused by various factors like environmental exposure or errors during DNA replication. Mutations can have a wide range of effects, from being harmless to causing diseases.