Breaking News
October 19, 2018 - Beckman Coulter Life Sciences announces new research-focused website
October 19, 2018 - Study finds link between refined soluble fibers, gut microbiota and liver cancer
October 19, 2018 - Social media reduces risk of depression among seniors with pain
October 19, 2018 - Newly developed synthetic DNA molecule may one day be used as ‘vaccine’ for prostate cancer
October 19, 2018 - Preoperative weight loss may not provide health benefits after surgery
October 19, 2018 - U.S. Birth Rates Continue to Drop as Age of New Moms Rises
October 19, 2018 - New technology can keep an eye on babies’ movements in the womb
October 19, 2018 - Juul e-cigarettes pose addiction risk for young users | News Center
October 19, 2018 - Gene sequencing reveals crucial molecular aspects of Trypanosoma brucei
October 19, 2018 - New DNA vaccine strategy protects mice against lethal challenge by multiple H3N2 viruses
October 19, 2018 - Study shows close link between cytokine interleukin-1ß and obesity-promoted colon cancer
October 19, 2018 - Muscle mass plays a critical role in health, shows research
October 19, 2018 - Study finds undiagnosed prediabetes in many infertile men
October 19, 2018 - The Current issue of “The view from here” is concerned with Nanotherapeutic strategies
October 19, 2018 - Delay in replacing the Pap smear with HPV screening is costing lives
October 19, 2018 - Physicians battle pediatric diseases of ear, nose, throat in Zimbabwe | News Center
October 19, 2018 - Researchers investigate why some cancers affect only young women
October 19, 2018 - Drugmakers funnel millions to lawmakers; a few dozen get $100,000-plus
October 19, 2018 - Unselfish people tend to have more children and receive higher salaries
October 19, 2018 - New findings reveal potential cellular players in tumor microenvironment
October 19, 2018 - Human brain cell transplant offers insights into neurological conditions
October 19, 2018 - Parental education associated with increased family health care spending
October 19, 2018 - New statistical method estimates long- and short-term risk of recurrence of breast cancer in US women
October 19, 2018 - Father’s exposure to nicotine may cause cognitive deficits in descendants
October 19, 2018 - Could we prevent Alzheimer’s disease by treating herpes?
October 19, 2018 - Nurse-led care can be more successful in managing gout
October 19, 2018 - Trump administration, pharma exchange verbal volleys on drug-price transparency
October 19, 2018 - Duke researchers find way to detect blood doping in athletes
October 19, 2018 - Many primary care doctors are still prescribing sedative drugs for older adults
October 19, 2018 - Finger length can predict sexuality in women say researchers
October 19, 2018 - Study finds differences in side-effects experienced by male and female OG cancer patients
October 19, 2018 - Few Seniors Who Self-Harm Referred for Mental Health Care
October 19, 2018 - Don’t sweat the sweet stuff
October 19, 2018 - URMC researchers discover new approach to deliver therapeutics to the brain
October 19, 2018 - Middlemen suppliers can increase drug prices and hospital bills, say Johns Hopkins researchers
October 19, 2018 - Bliss funds research to find whether parental touch can help alleviate pain in premature infants
October 19, 2018 - Human neurons employ highly compartmentalized signaling, study shows
October 19, 2018 - Ultromics expands multiple clinical trials for coronary heart disease to the U.S.
October 19, 2018 - $11 million NIH grant for Clemson University helps launch new center for musculoskeletal research
October 19, 2018 - A new approach identified to control Zika virus, dengue fever
October 19, 2018 - Head Blows Without Concussion May Not Damage Brain, Study Claims
October 19, 2018 - US opioid use not declined, despite focus on abuse and awareness of risk
October 19, 2018 - Next-generation RNA sequencing technology sheds new light on human mitochondrial diseases
October 19, 2018 - UT Southwestern biochemist receives 2019 Breakthrough Prize in Life Sciences for innate immunity discovery
October 19, 2018 - The immune system also plays a key role in day-to-day function of healthy organs
October 19, 2018 - New tool may reveal how the brain structure impacts brain activity, human behavior
October 19, 2018 - Trump Administration announces ‘Winning on Reducing Food Waste’ initiative
October 19, 2018 - For-profit nursing home residents more likely to experience health issues caused by substandard care
October 19, 2018 - Incidence of stroke has risen steadily among marijuana users, show studies
October 19, 2018 - Conceptual framework proposed to examine role of exercise in multiple sclerosis
October 19, 2018 - Near infrared spectroscopy technique for accurate evaluation of chondral injuries
October 19, 2018 - Scientists receive $5.1 million grant to develop stem cell-based therapy for blinding retinal conditions
October 19, 2018 - Shorter physician encounters associated with antibiotic prescribing
October 19, 2018 - In the Spotlight: Enjoying research and exploring opportunities
October 19, 2018 - Physical activity lowers cardiovascular mortality risk in frail older adults
October 19, 2018 - New imaging tool helps visualize how sound-induced vibrations travel through the ear
October 19, 2018 - Key insights into the application, production of bioactive materials
October 19, 2018 - New urea sorbent could speed up the development of wearable artificial kidney
October 19, 2018 - Intensive care patients’ muscles less able to use fats for energy
October 19, 2018 - FDA Advisory Committee Recommends Approval of Dsuvia for the Treatment of Moderate-to-Severe Acute Pain
October 19, 2018 - 48,XXXY syndrome – Genetics Home Reference
October 19, 2018 - Physical exercise improves the elimination of toxic proteins from muscles
October 19, 2018 - How a new system improved wait times for Stanford kidney transplant patients
October 19, 2018 - Nutrition has bigger positive impact on bone mass and strength than exercise
October 19, 2018 - Study finds lack of progress in media representation of nurses over last 20 years
October 19, 2018 - Many people have trouble understanding differences between OCD and OCPD
October 19, 2018 - New family planning app found to be as effective as modern methods
October 19, 2018 - Gastric Banding, Metformin Similar for Improving Glycemia
October 19, 2018 - Physiologist publishes findings on the role of the protein titin in muscle contraction
October 19, 2018 - What digital health companies need to do to succeed
October 19, 2018 - N. Carolina Sees Alarming Spike in Heart Infections Among Opioid Users
October 19, 2018 - Video monitoring of TB therapy works well in urban and rural areas
October 19, 2018 - Determining acid-neutralizing capacity for OTC antacids
October 19, 2018 - Males who spend more time taking care of kids have greater reproductive success
October 18, 2018 - Study to explore bioethics of brain organoids
October 18, 2018 - Environmental conditions may drive development of multiple sclerosis
October 18, 2018 - Genetically modifying zebrafish provides more accurate disease models
October 18, 2018 - Purdue Pharma, Eisai announce positive topline results from Phase 3 study of lemborexant
October 18, 2018 - 5 Strength-Training Mistakes to Avoid
October 18, 2018 - Immune system’s balancing act keeps bowel disease in check
New findings point to potential therapy for Parkinson’s Disease

New findings point to potential therapy for Parkinson’s Disease

image_pdfDownload PDFimage_print
Partial inhibition of the interaction between calcineurin and FKBP12, with low doses of the FDA-approved compound Tacrolimus, protect neurons against the toxic effects of a-synuclein, a protein critically implicated in Parkinson’s disease. Credit: Northwestern University

A new study, published in Proceedings of the National Academy of Sciences (PNAS), sheds light on a mechanism underlying Parkinson’s disease and suggests that Tacrolimus—an existing drug that targets the toxic protein interaction explored in the study—could be used as a novel treatment.

Gabriela Caraveo Piso, Ph.D., assistant professor of Neurology in the Division of Movement Disorders, was the first and corresponding author of the study.

Parkinson’s disease is a progressive neurological disorder marked by the loss of dopaminergic neurons. There is no cure, and current treatments to help control the symptoms of Parkinson’s—including tremor, slow movement and loss of balance—are limited.

Although the fundamental cause of Parkinson’s disease is unknown, dysfunction of a protein called alpha-synuclein has long been thought to play an important role.

Previous investigations by Caraveo Piso and collaborators had established that increased activity of an enzyme called calcineurin is associated with the alpha-synuclein toxicity seen in Parkinson’s.

In the current study, the scientists built upon those discoveries to demonstrate, for the first time, that a protein called FKBP12 is a major regulator of calcineurin activity, and thus contributes to alpha-synuclein toxicity.

“Our new mechanistic findings have revealed that FKBP12 is the protein that tunes calcineurin activity,” Caraveo Piso said. “It’s very reminiscent of the Goldilocks story: In the context of alpha-synuclein, both too much and no calcineurin activity are detrimental—but an intermediate level of activity is protective.”

The scientists also investigated whether reducing the functional interaction between calcineurin and FKBP12 might be protective against alpha-synuclein toxicity in vivo.

To do so, they employed an already well-established, FDA-approved inhibitor of this interaction, called Tacrolimus. The drug is currently used clinically in high doses to prevent organ rejection after a transplant, a process in which calcineurin also plays a critical role.

In an animal model of Parkinson’s disease, the investigators demonstrated that Tacrolimus—when administered in low doses to achieve partial reduction of calcineurin activity—led to improvements in the functional features of dopaminergic neurons, and hence behavioral phenotypes.

Caraveo Piso noted that the discovery has strong potential for future clinical applications.

“We provide robust animal evidence for a feasible treatment against Parkinson’s by repurposing Tacrolimus at low, sub-immunosuppressive doses,” Caraveo Piso said. “Since Tacrolimus has high brain penetrance and can be given safely, a clinical trial of Tacrolimus in patients with early-stage Parkinson’s would likely pose no serious logistical or regulatory difficulties.”

The findings might also have implications for other related neurological diseases, such as Alzheimer’s, Caraveo Piso notes, an area where calcineurin also plays an important role.


Explore further:
Tug of war between Parkinson’s protein and growth factor

More information:
Gabriela Caraveo et al. FKBP12 contributes to α-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1711926115

Journal reference:
Proceedings of the National Academy of Sciences

Provided by:
Northwestern University

Tagged with:

About author

Related Articles