About My Health Careers Internship MedBlogs Contact us
Medindia LOGIN REGISTER
Advertisement

New Insights into the Progression of Parkinson’s Disease

by Anjali Aryamvally on March 6, 2018 at 4:58 PM
Font : A-A+

New Insights into the Progression of Parkinson’s Disease

A connection between neuronal death and Lewy bodies in Parkinson's disease has been discovered by a research team at The Scripps Research Institute (TSRI). The study published in the journal Proceedings of the National Academy of Sciences, offers an explanation for why neurons die off in the first place.

An estimated 10 million people worldwide are living with Parkinson's disease--an incurable neurodegenerative disorder that leads to an increasing loss of motor control.

Advertisement


If we could peer into the brains of these patients, we'd see two hallmarks of the disease. First, we'd see a die-off of the brain cells that produce a chemical called dopamine. We'd also see protein clumps called Lewy bodies inside the neurons.

Corinne Lasmézas, DVM, PhD, a professor on the Florida campus of The Scripps Research Institute (TSRI), believes a key to treating Parkinson's is to study possible links between these two phenomena.
Advertisement

'This study identifies the missing link between Lewy bodies and the type of damage that's been observed in neurons affected by Parkinson's," says Lasmézas, senior author of the study. "Parkinson's is a disorder of the mitochondria, and we discovered how Lewy bodies are releasing a partial break-down product that has a high tropism for the mitochondria and destroys their ability to produce energy."

Toxic protein travels to mitochondria to do damage

Lewy bodies were described a century ago, but it was not until 1997 that scientists discovered they were made of clumps of a misfolded protein called α-synuclein. When it's not misfolded, α-synuclein is believed to carry out functions related to the transmission of signals between neurons.

Lasmézas' research focuses on neurological disorders caused by misfolded proteins, such as Alzheimer's, Parkinson's, prion diseases, frontotemporal dementia and amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). She uses lab models, including cell cultures and mice, to study these diseases.

In the current study, Lasmézas and her team looked at cell cultures of neurons that were induced to accumulate fibrils made of misfolded α-synuclein, mimicking Lewy bodies in patients with Parkinson's. They discovered that when α-synuclein fibrils are broken down, it often creates a smaller protein clump, which they named pα-syn* (pronounced "P-alpha-syn-star").

"Sometimes the nerve cells can efficiently degrade the α-synuclein fibrils, but if they get overwhelmed, the degradation may be incomplete," she explains. "And it turns out that the result of that partial degradation, pα-syn*, is toxic."

Diego Grassi, PhD, a research associate in Lasmézas' lab, made this discovery by labeling the pα-syn* with an antibody so he could follow it throughout the cell after it was created. He observed that pα-syn* traveled and attached itself to the mitochondria. Further investigation revealed that once the pα-syn* attached, the mitochondria started to break down. These fragmented mitochondria lose their ability to carry an electrochemical signal and produce energy.

The researchers followed up with an analysis of mouse and human brain samples. They confirmed the existence of pα-syn* in the dopamine-producing neurons.

"The Lewy bodies are big aggregates and they're sitting in the cell, but they don't come into direct contact with the mitochondria in the way pα-syn* does," Lasmézas explains. "With Diego's discovery, we've made a direct connection between the protein α-synuclein and the downstream effects that are observed when brain cells become damaged in Parkinson's."

Lasmézas plans to continue studying the connection between misfolded proteins and the destruction of mitochondria in neurons. "What we found may not be the only mechanism of toxicity, but we know it's important," she says. "This paper is about identifying where pα-syn* comes from and what it does to the mitochondria, but there's obviously, mechanistically, a lot that we still don't know."

She says that these findings also have implications for designing treatments for Parkinson's, noting that some drugs currently under development are focused on getting rid of larger fibrils that make up Lewy bodies.

"It's important to be aware that when Lewy bodies are broken down, these toxic substances may be created," Lasmézas says. In addition, she adds, the discovery of pα-syn* as an important component of the disease process points to a new target for creating drugs slowing disease progression.



Source: Eurekalert
Advertisement

Advertisement
News A-Z
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Advertisement
News Category
What's New on Medindia
International Day of Persons with Disabilities 2021 - Fighting for Rights in the Post-COVID Era
Effect of Blood Group Type on COVID-19 Risk and Severity
Woman with Rare Spinal Cord Defect from Birth Sues Doctor
View all

Medindia Newsletters Subscribe to our Free Newsletters!
Terms & Conditions and Privacy Policy.

More News on:
Nutritional Management of Parkinsons disease 

Recommended Reading
New Insights into Parkinson’s Treatment
One of the factors behind nerve cell death in Parkinson's disease identified, unlocking the ......
Brain Device with 25 Years Battery Life
Implanting a brain device for Parkinsons disease to treat diseases with abnormal brain stimulation ....
Existance of Neurological Diseases Spotted by Brainwave Markers
COGNISION system can be used to detect brainwave markers that point to the existence of certain ......
Make Treatment of Parkinsons More Affordable, Doctors Plead
The Parkinson's disease occurs when certain nerve cells in the brain, called the substantia nigra, ....
Nutritional Management of Parkinsons disease
Parkinson's disease is a brain disorder which leads to many other related effects. Nutrition plays a...

Disclaimer - All information and content on this site are for information and educational purposes only. The information should not be used for either diagnosis or treatment or both for any health related problem or disease. Always seek the advice of a qualified physician for medical diagnosis and treatment. Full Disclaimer

© All Rights Reserved 1997 - 2021

This site uses cookies to deliver our services. By using our site, you acknowledge that you have read and understand our Cookie Policy, Privacy Policy, and our Terms of Use