Volume 2, Issue 11
Glowing Research on Brain Diseases
Christopher Chang received a prestigious 2005 Beckman Young Investigator award.
Growing old can be scary. An estimated 4.5 million Americans have Alzheimer's disease and two million suffer from Parkinson's disease. As the population ages and life expectancy increases, the number of people with neurodegenerative diseases will skyrocket. For example, the Alzheimer's Association predicts that by 2050, as many as 16 million people could have the disease. UC Berkeley chemistry professor Chris Chang is developing novel optical probes that may shed light on how neurodegenerative diseases slowly devastate the brain. Eventually, these insights could aid in the quest for new treatments.
"We don't know many of the causative reasons for these diseases, but we can see their effect on the brain at the end," Chang says. "We'd like to see from a cellular level what mechanisms are involved in the processes of the disease."
While the symptoms of Alzheimer's, Parkinson's and other neurodegenerative diseases are very different, their pathology is similar. Metals like iron, copper, and zinc are essential nutrients in the brain. However, pools of these metals are found gumming up the brains of patients with Alzheimer's and other diseases. These plaque-like deposits, and also damage from oxidation, are implicated in neurodegenerative diseases.
"If you're healthy, you have a lot of metal ions but they're sequestered and functioning normally," Chang says. "If you have one of these diseases, the metal ion levels are elevated and the associated proteins are not working correctly. Somewhere in the middle though is the black box, and that's the important part to observe."
Last year, the researchers demonstrated a selective, cell-permeable optical probe that fluoresces green in the presence of hydrogen peroxide.
The aim, Chang explains, is to develop methods for imaging the metal ions and related chemistry within living cells and tissues in real time. Traditional magnetic resonance imaging (MRI) technology used for brain scans can't deliver the cellular resolution necessary to detect the chemical signposts of neurodegenerative disease.
Chang and his colleagues are developing fluorescent chemical probes that act as tags for certain analytes such as metal ions or metabolites that indicate oxidation. The idea is that a physician could inject a patient with a chemical probe that would seek out those targets. Once the probe recognized the specific analyte nearby, a chemical bond would be made or broken, causing the tag's fluorescence to "switch on." Then, an infrared beam of light would reveal the location of the tags in the brain.
"It would be completely non-invasive and the subject wouldn't need to lie perfectly still as they do with MRI to get a good visualization," Chang says.
Already, the researchers have reported success in vitro with a probe that selectively reacts with the oxidant hydrogen peroxide. Their current probes are illuminated using visible light. The next step is to move to infrared wavelengths that can penetrate through bone, skin, and tissue for real world in vivo applications. According to Chang, the long-term goal is to develop a cocktail of probes that can be hit with many wavelengths of light to simultaneously observe a handful of different markers. The ability to image the cellular chemistry of neurodegenerative diseases and correlate those reactions to the progression of symptoms could help unravel mysteries about how the brain works and how it can fail.
"With the population getting older, these are the diseases we need to pay more attention to," Chang says. "Basic research has to start today in order to be ready for these types of problems tomorrow."