Like Origami Paper, Proteins Must Be Folded Correctly

In Origami, 2-D pieces of paper can be folded into 3-D masterpieces. 

A protein is a linear sequence of amino acids linked together through peptide bonds. Proteins differ in the sequence of the twenty different amino acids that our cells assemble, and in their length. However, to function properly, the 1-D protein has to be correctly folded into a 3-D structure.

Hemoglobin (below) is the oxygen-carrying protein in our bloodstream, but it cannot carry oxygen unless its linear structure is folded properly. When a protein misfolds, it becomes toxic. Unlike other cells in the body, neurons cannot dilute the toxin by rapidly dividing. Misfolded proteins clog up transportation systems in neurons and cause them to die.

Each of the progressive neurodegenerative diseases is characterized by different proteins which misfold. Our strategy in developing new therapies for ALS, Alzheimer’s, and Parkinson’s is to find drugs that stop protein misfolding. We discovered that the amino acid L-serine helps to prevent protein misfolds.

A New Approach to Parkinson’s Disease Therapy

David Long

Lewy bodies, formed from misfolded α-synuclein protein, are the neuropathological feature of Parkinson’s disease. While levodopa can help control symptoms, no current Parkinson’s medication slows disease progression.

 We attempted to produce Lewy bodies in vivo but did not have enough funds to continue the experiments. Enter Ty and Sue Measom of Logan, Utah, and Fred and Candy Berthrong of Providence, Utah who provided a generous gift to complete the study in which we found that BMAA triggers Lewy bodies in marmosets.

 We were unable to begin a second study until the philanthropic torch was picked up by Robert and Robin Paulson and Stan and Mary Seidler of Jackson Hole. They provided the lead gifts to determine if L-serine or L-tyrosine can slow Lewy body formation.

A generous pledge from David and Lisa Long of Lake Forest, Illinois allowed us to accelerate the project. Our colleagues at NeuroScience Associates in Tennessee assisted us by giving a significant discount on the regular fees for state-of-the-art sectioning and staining of the tissues. We still have $100,000 to raise to finish the project but are proceeding at full speed.

Because of the generous donors who helped us, including Bobbie Sweet, John Madigan, and James and Ellen Walton, we will have the final results in February 2022. If successful, this new drug will remain a lasting legacy for David Long who passed away on September 19, 2021.