What is ubiquitin

A protein family important in the sequence of events, called the ubiquitin protea-some system, through which cells eliminate the waste by-products of their functions. The Latin word ubique means “everywhere,” an apt foundation for this protein’s name. Nearly all cells in the human body contain ubiquitin, and ubiquitin is the most prevalent protein in the brain. Malfunctions of the ubiquitin proteasome system allow protein molecules to accumulate within cells, where they can disrupt normal cell functions and damage and even kill the cell. Genes regulate ubiquitin synthesis (production) and function. Scientists have discovered a number of mutations in the genes that regulate ubiquitin in people with neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease, suggesting that there are connections between malfunctioning ubiquitin processes and the accumulations of proteins such as tau (in Alzheimer’s, cortical-basal ganglionic degeneration, and progressive supranuclear palsy) and alpha-synuclein (in Parkinson’s, multiple system atrophy, and Lewy body dementia) that characterize these diseases.

The Ubiquitin Proteasome System

The ubiquitin proteasome system is an intricate, and not yet completely understood, process through which cells identify and “tag” molecules they no longer need. These molecules may be the waste by products of the cell’s metabolic function, or molecules that have aged beyond their ability to be functional. It appears that there is a sequence of tagging, or ubiquitin encoding, that takes place. When the right encoding tags a molecule, an enzyme structure called a proteasome (“protein body”) interacts with the molecule and degrades it (takes it apart). The ubiquitin molecules attached to the molecule seem also to participate in this degradation, although scientists are not certain of their roles. The cell then recycles the component particles to feed its adenosine triphosphate (ATP) energy production needs and to perform other cell functions.

Researchers do not know how much of the ubiquitin proteasome system is genetic and how much is environmental (influenced by cell activity). They do know that when the system malfunctions, damaged and ineffective protein molecules remain within the cell. This molecular clutter eventually interferes with the cell’s ability to function, damaging the entire cell or leading to its death. Ubiquitin also has roles in repair of cell deoxyribonucleic acid (DNA), in mitochondrial metabolism, and in the process of apoptosis (programmed cell death), although the precise nature of this involvement also is among the aspects of ubiquitin’s function that scientists do not fully understand.

Ubiquitin, Alpha-Synuclein, and Parkin

Although Parkinson’s lewy bodies predominantly contain alpha-synuclein, they also contain parkin and ubiquitin. The ubiquitin genes, which regulate the body’s production and use of ubiquitin, exist in close proximity to genes that regulate various protein functions linked to Parkinson’s (parkin and alpha-synuclein) and Alzheimer’s (tau). Some scientists suspect that mutations of these genes are interrelated and affect the functioning of all of these proteins. Others believe that ubiquitin gene mutations affect only the ways in which ubiquitin functions to tag and degrade other proteins, including alpha-synuclein and tau; that it is a malfunction of ubiquitin tagging that allows these proteins to accumulate as the deposits found in the tau entanglements of Alzheimer’s disease and the lEwy bodies of Parkinson’s disease; and that other factors (genetic and environmental) determine the disease process that results.