Regulation of Parkinson’s disease inflammatory responses by a microRNA
by Jeff Hansen
A small regulatory RNA called microRNA-155 appears to play a key role in the brain inflammation that helps foster Parkinson’s disease. This finding, using a mouse model, implicates microRNA-155 as both a potential therapeutic target and biomarker for this progressive neurodegenerative disorder, according to a University of Alabama at Birmingham study published Feb. 23 in The Journal of Neuroscience.
Parkinson’s disease, the most common neurodegenerative movement disorder, affects as many as 1 million Americans, more than multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease combined. About 60,000 new U.S. cases are diagnosed each year, and thousands more go undetected.
Parkinson’s disease can progress undetected for years before symptoms appear. The UAB researchers, led by David Standaert, M.D., Ph.D., professor and chair of the UAB Department of Neurology, write that their results “suggest that microRNA-155 is involved early in Parkinson’s disease pathogenesis and is important for initiating the inflammatory response to alpha-synuclein.”
Widespread intracellular aggregates of alpha-synuclein protein, or α-syn, are a hallmark of Parkinson’s disease, along with progressive loss of neurons in a region of the brain called the substantia nigra pars compacta, or SNpc.
The mouse model used by the UAB team uses a virus to deliver a human α-syn gene to the brain, where it is overexpressed, leading to inflammation and neurodegeneration. The researchers examined whether this overexpression α-syn also changed expression of any microRNAs. MicroRNAs — which interact with messenger RNAs after their export from the cell nucleus — act to regulate gene expression in cells, and there are more than 1,300 distinct microRNAs at work in the brain.
The UAB researchers probed with an array of 84 inflammation- and autoimmune-associated microRNAs and found that microRNA-155 was significantly overexpressed in the SNpc, two weeks after viral delivery of the α-syn gene.
To see whether microRNA-155 was involved in inflammation and neurodegeneration, they tested mice with a deletion of the microRNA-155 gene. In the mouse α-syn model, this deletion prevented the increased expression two immune-cell markers — MHCII and CD68 — in the SNpc. Similarly, knock-out of the microRNA-155 gene prevented the α-syn-associated neurodegeneration that is seen six months later in wild-type mice challenged with α-syn.
The toll of Parkinson’s
“Our studies suggest,” the authors wrote, “that microRNA-155 is a key inflammation-initiating molecule that could be a viable target for Parkinson’s disease therapeutics.”
Authors of the paper, “MicroRNA-155 Regulates Alpha-Synuclein-Induced Inflammatory Responses in Models of Parkinson Disease,” are Aaron D. Thome, Ashley S. Harms, Laura A. Volpicelli-Daley and David G. Standaert, all of the Center for Neurodegeneration and Experimental Therapeutics, UAB Department of Neurology.
The work was supported by the American Parkinson Disease Association, and NIH grants F31 NS084722 and P20 NS092530.
UAB’s Roberson joins celebrity chef B. Smith for a discussion on Alzheimer’s disease at local book signing
|B. Smith — restaurateur, magazine publisher, celebrity chef and nationally known lifestyle maven — and her husband, Dan Gasby, will visit the Barnes & Noble store at The Summit in Birmingham for a special event to discuss and sign copies of their book, “Before I Forget,” written with Vanity Fair contributing editor Michael Shnayerson. Smith has been diagnosed with Alzheimer’s disease, and “Before I Forget” describes her and Gasby’s journey with the disease and offers practical advice about dealing with Alzheimer’s day-to-day challenges, the family realities and tensions, ways of coping, and lessons learned along the way.
Erik Roberson, M.D., Ph.D., Virginia B. Spencer Professor of Neuroscience and director of the Alzheimer’s Disease Center at the University of Alabama at Birmingham School of Medicine, will participate in the discussion to share research on the disease and answer questions from the audience.
The event is at 7 p.m., Tuesday, Feb. 23, at the Barnes & Noble at The Summit, 201 Summit Blvd., Suite 100.
By Bob Shepard
UAB Media Relations
UAB’s King honored by Alabama ALS chapter
|Peter King, M.D., professor in the Department of Neurology in the School of Medicine at the University of Alabama at Birmingham, will receive the 2016 Spirit of Lou Gehrig Award from the ALS Association’s Alabama Chapter. King has spent 20 years treating patients with the disease and is a leading researcher working to find a cure for ALS. Amyotrophic lateral sclerosis is a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord. The disease robs victims of the ability to walk, talk and eventually even blink an eye.
King will receive the award at the second annual “Changing the Game” awards dinner, 6 p.m. Wednesday, Feb. 24, at The Club on Robert Smith Drive in Birmingham. Guest speakers at the event will be former Auburn great Bo Jackson and former University of Alabama star Tony Nathan.
The award is named for baseball player Lou Gehrig, nicknamed “the Iron Horse.” Gehrig showed extraordinary courage and commitment to the game of baseball in the face of a devastating ALS diagnosis.
For more information about The ALS Association Alabama Chapter and the “Changing the Game” event, visit www.alsalabama.org or www.changingthegameALS.org.
ROCK’n the Tau Pathway?
A kinase inhibitor that is an approved medication for people and improves memory in rats also promotes degradation of toxic tau in lab models, according to a paper in the January 27 Journal of Neuroscience. Inhibiting the Rho-associated protein kinases ROCK1 and ROCK2 with the drug fasudil got rid of tau in cultured human neurons and the eyes of fruit flies, report senior author Jeremy Herskowitz and colleagues from the University of Alabama in Birmingham. Fasudil is a vasodilator approved in Japan and China to prevent tightening of arteries and ischemia following surgery in the subarachnoid space surrounding the brain. It has undergone preclinical investigation in several neurodegenerative conditions thanks to its effects on autophagy and inflammation. The drug, or related compounds, might be more broadly applicable to prevent a variety of tauopathies, Herskowitz suggested. Alas, efforts to study fasudil in those diseases have been limited thus far.
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