Featured Research

from universities, journals, and other organizations

Synergistic interaction enhances pathogenesis of Parkinson's disease

Date:
December 24, 2009
Source:
Cell Press
Summary:
Scientists have identified a synergistic interaction that disrupts normal intracellular transport mechanisms and leads to the accumulation of neuron-damaging clumps of protein associated with Parkinson's disease (PD), a neurodegenerative disorder that is characterized by a specific loss of neurons in the midbrain and brainstem. The research identifies a new potential therapeutic option for preventing PD-associated neuropathology.

Scientists have identified a synergistic interaction that disrupts normal intracellular transport mechanisms and leads to the accumulation of neuron-damaging clumps of protein associated with Parkinson's disease (PD), a neurodegenerative disorder that is characterized by a specific loss of neurons in the midbrain and brainstem. The research, published by Cell Press in the December 24 issue of the journal Neuron, identifies a new potential therapeutic option for preventing PD-associated neuropathology.

Related Articles


Mutations in the alpha--synuclein (α-syn) and Leucine-rich repeat kinase (LRRK2) genes have been linked with inherited and sporadic forms of PD and previous research has shown that accumulation of cytotoxic α-syn protein inside of neurons represents a key step in the pathogenesis of PD. "Although earlier studies have suggested interplay between α-syn and LRRK2, a synergistic interaction in the pathogenesis of PD has not been established," explains senior study author Dr. Huaibin Cai from the Laboratory of Neurogenetics at the National Institutes of Health in Bethesda, Maryland.

In order to systematically investigate whether LRRK2 and α-syn act synergistically to potentiate PD, Dr. Cai and colleagues generated and characterized several types of transgenic mice that overexpressed different combinations of a PD-related alpha-syn mutation along with various forms of normal and PD-associated LRRK2. The researchers found that although overexpression of LRRK2 alone did not cause neurodegeneration, excess LRRK2 significantly accelerated the progression of neuropathological abnormalities in transgenic mice expressing PD-related α-syn.

Overexpression of LRRK2 disrupted key structures and mechanism that play a role in transporting proteins inside of the neurons. Importantly, genetic disruption of LRRK2 maintained normal intracellular transport and reduced the accumulation of α-syn, thereby significantly delaying the progression of PD pathology in the PD α-syn transgenic mice. These findings suggest that LRRK2 exacerbates the abnormal intracellular accumulation of α-syn.

"We have uncovered a novel function for LRRK2 in regulating the intracellular trafficking and accumulation of α-syn in neurons and our results suggest that excessive amounts of LRRK2 or its mutants may result in abnormal neuron-damaging accumulation of α-syn protein," concludes Dr. Cai. "It is possible that inhibition of LRRK2 expression may provide an applicable therapeutic strategy to ameliorate α-syn-induced neurodegeneration in PD or other related neurodegenerative diseases."

The researchers include Xian Lin, National Institute on Aging, National Institutes of Health, Bethesda, MD; Loukia Parisiadou, National Institute on Aging, National Institutes of Health, Bethesda, MD; Xing-Long Gu, National Institute on Aging, National Institutes of Health, Bethesda, MD; Lizhen Wang, National Institute on Aging, National Institutes of Health, Bethesda, MD; Hoon Shim, National Institute on Aging, National Institutes of Health, Bethesda, MD; Lixin Sun, National Institute on Aging, National Institutes of Health, Bethesda, MD; Chengsong Xie, National Institute on Aging, National Institutes of Health, Bethesda, MD; Cai-Xia Long, National Institute on Aging, National Institutes of Health, Bethesda, MD; Wan-Jou Yang, National Institute on Aging, National Institutes of Health, Bethesda, MD; Jinhui Ding, National Institute on Aging, National Institutes of Health, Bethesda, MD; Zsu Zsu Chen, University of Alabama at Birmingham, Birmingham, AL; Paul E. Gallant, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Jung-Hwa Tao-Cheng, National Institutes of Health, Bethesda, MD; Gay Rudow, The Johns Hopkins University School of Medicine, Baltimore, MD; Juan C. Troncoso, The Johns Hopkins University School of Medicine, Baltimore, MD; Zhihua Liu, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Zheng Li, National Institute of Mental Health, National Institutes of Health, Bethesda, MD; and Huaibin Cai, National Institute on Aging, National Institutes of Health, Bethesda, MD.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Synergistic interaction enhances pathogenesis of Parkinson's disease." ScienceDaily. ScienceDaily, 24 December 2009. <www.sciencedaily.com/releases/2009/12/091223125121.htm>.
Cell Press. (2009, December 24). Synergistic interaction enhances pathogenesis of Parkinson's disease. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2009/12/091223125121.htm
Cell Press. "Synergistic interaction enhances pathogenesis of Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2009/12/091223125121.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins