Learning how the brain takes out its trash may help decode neurological diseases

Imagine that garbage haulers don’t exist. Slowly, the trash accumulates in our offices, our homes, it clogs the streets and damages our cars, causes illness and renders normal life impossible. Garbage in the brain, in the form of dead cells,…

Imagine that garbage haulers don’t exist. Slowly, the trash accumulates in our offices, our homes, it clogs the streets and damages our cars, causes illness and renders normal life impossible.

Garbage in the brain, in the form of dead cells, must also be removed before it accumulates, because it can cause both rare and common neurological diseases, such as Parkinson’s. Now, University of Michigan researchers are a leap closer to decoding the critical process of how the brain clears dead cells, said Haoxing Xu, associate professor in the U-M Department of Molecular, Cellular and Developmental Biology.

A new U-M study identified two critical components of this cell clearing process: an essential calcium channel protein, TRPML1, that helps the so-called garbage collecting cells, called microphages or microglia, to clear out the dead cells; and alipid molecule, which helps activate TRPML1 and the process that allows the microphages to remove these dead cells.

Moreover, the Xu lab identified a synthetic chemical compound that can activate TRPML1. Because this chemical compound ultimately helps activate this cell-clearing process, it provides a drug target that could help combat these neurological diseases.

“This is clearly a drug target,” Xu said. “What this paper picks out is exactly what is going wrong in this process.”

Scientists began by looking at a very rare neurodegenerative disease called Type IV Mucolipidosis, a childhood neurodegenerative disease characterized by multiple disabilities.

Xu’s group found that lack of TRPML1 function, which is the channel through which calcium is released from the lysosome — the cell’s recycling center — into the microphage cells, contributes to these neurodegenerative conditions. If this calcium channel doesn’t work, calcium cannot be released, and dead cells aren’t removed, Xu said. The synthetic chemical compound stimulates the TRPML1 calcium channel to release the calcium into the cell.
Further, dead cells “are bad for live cells,” Xu said. An excess of dead cells leads the macrophage cells to also kill healthy neurons necessary for neurological function, which in turn can lead to these neurodegenerative diseases.
There are many neurodegenerative diseases, some very rare and some more common, such as Parkinson’s and ALS. The common thread among them is the dearth of live and functioning neurons, which prevents the neurological system from carrying out normal functions, Xu said.
Thus, identifying a lipid molecule and also chemical compounds that stimulates proper function of the TRMPL1 function could revolutionize the treatment of these neurodegenerative diseases.
The next step in Xu’s research is to test how these general observations are helpful to the neurological diseases and whether the compound is effective in animal models of neurological diseases.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

Story Source:

The above story is based on materials provided by University of Michigan.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.

Journal Reference:
Mohammad Samie, Xiang Wang, Xiaoli Zhang, Andrew Goschka, Xinran Li, Xiping Cheng, Evan Gregg, Marlene Azar, Yue Zhuo, Abigail G. Garrity, Qiong Gao, Susan Slaugenhaupt, Jim Pickel, Sergey N. Zolov, Lois S. Weisman, Guy M. Lenk, Steve Titus, Marthe Bryant-Genevier, Noel Southall, Marugan Juan, Marc Ferrer, Haoxing Xu. A TRP Channel in the Lysosome Regulates Large Particle Phagocytosis via Focal Exocytosis. Developmental Cell, 2013; DOI: 10.1016/j.devcel.2013.08.003

Note: If no author is given, the source is cited instead.

Search ScienceDaily
Number of stories in archives: 142,244

 

Interested in ad-free access? If you’d like to read ScienceDaily without ads, let us know!

more breaking science news

Social Networks
Follow ScienceDaily on Facebook, Twitter, and Google:

Recommend ScienceDaily on Facebook, Twitter, and Google +1:

Other social bookmarking and sharing tools:

Breaking News
… from NewsDaily.com

more science news
In Other News …
more top news
Science Video News

Turning Trash Into Power
A new kind of waste digester uses two different strains of bacteria in different tanks. This would normally take place in the same environment, but. …  > full story

Strange Science News
Free Subscriptions
… from ScienceDaily

Get the latest science news with our free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:
Email Newsletters
RSS Newsfeeds
Feedback
… we want to hear from you!

Tell us what you think of ScienceDaily — we welcome both positive and negative comments. Have any problems using the site? Questions?
Leave Feedback