Breaking News
August 15, 2018 - College students may experience pressures from secondary exposure to opioid abuse
August 15, 2018 - Powerful new microscope reveals inner workings of human cells with unprecedented clarity
August 15, 2018 - Married people who fight nastily more likely to suffer from leaky guts, study suggests
August 15, 2018 - Working Out After Baby – Drugs.com MedNews
August 15, 2018 - Rheumatoid Factor (RF) Test: MedlinePlus Lab Test Information
August 15, 2018 - ADHD linked to an increased risk of injury in children, study finds
August 15, 2018 - UIC researchers receive NIH funding to develop a better way to regenerate bone or tissues
August 15, 2018 - Study reveals how immune cells in the brain influence sexual behavior
August 15, 2018 - Researchers move closer to finding potential soft spot in drug-resistant tuberculosis
August 15, 2018 - Real-time dynamic monitoring of cell’s nucleus for effective cancer screening
August 15, 2018 - Lower rates of Medicare preventive care visits found in racial, ethnic minority older adults
August 15, 2018 - Scientists identify stress hormone as key factor in failure of immune system to inhibit leukemia
August 15, 2018 - Cytoplan introduces three new nutritional supplements
August 15, 2018 - Effective hemorrhage control critical for survival after motorsport accidents
August 15, 2018 - Sygnature Discovery announces ambitious expansion plan with addition of Alderley Park facility
August 15, 2018 - Dietary carbohydrates could lead to osteoarthritis, new study finds
August 15, 2018 - Male tobacco smokers have decreased number of cannabinoid CB1 receptors, study reveals
August 15, 2018 - Scientists explore ways for drug therapies to reach deadly brain tumors
August 15, 2018 - Rethinking fundamental rule of stroke care: ‘Time is brain!’
August 15, 2018 - Scientists reveal role of ‘junk DNA’ in cancer dissemination
August 15, 2018 - Google’s DeepMind AI could soon be diagnosing eye conditions
August 15, 2018 - Scientists trick the brain to embody the prosthetic limb
August 15, 2018 - Researchers focus on uncoupling obesity from diabetes
August 15, 2018 - A class of proteins shown to be effective in reducing drug-seeking behaviors
August 15, 2018 - FundamentalVR launches first-of-its-kind SaaS software platform for surgical simulation
August 15, 2018 - Gemphire Announces Termination of Phase 2a Clinical Trial of Gemcabene in Pediatric NAFLD
August 15, 2018 - Rheumatoid arthritis in pregnancy associated with low birth weight and premature birth
August 15, 2018 - Study may help increase effectiveness of antibiotics against drug-resistant bacteria
August 15, 2018 - Analyzing resident-to-resident incidents in dementia may hold the key to reducing future fatalities
August 15, 2018 - Robotic walking frame aims to help maintain mobility of older adults
August 15, 2018 - Simple intervention during routine care reduces alcohol consumption in men with HIV
August 15, 2018 - Genetics Home Reference: gout
August 15, 2018 - Scientists ID genesis of disease, focus efforts on shape-shifting tau
August 15, 2018 - OncoThira and NDSU enter into license agreement to develop, market cancer compounds
August 15, 2018 - Scientists unravel the mystery behind ovarian cancer with high-grade serous carcinoma
August 15, 2018 - Common signs that indicate vision problems in children
August 15, 2018 - Removing the cancer label – overhaul in cancer classification proposed
August 15, 2018 - Prams may expose babies and toddlers to more air pollution finds study
August 15, 2018 - Duke researchers track missing T-cells in glioblastoma patients
August 15, 2018 - Cardiac Profiles Up With Exercise, Less Sitting in Early Old Age
August 15, 2018 - Precision medicine offers a glimmer of hope for Alzheimer’s disease
August 15, 2018 - Immunovia’s new blood-based testing platform accurately detects non-small cell lung cancer
August 15, 2018 - New method provides a ‘big picture’ of genetic influences on traits and diseases
August 15, 2018 - Early Onset Type 1 Diabetes Linked to Heart Disease, Shorter Life
August 14, 2018 - SMURF1 provides targeted approach to preventing cocaine addiction relapse
August 14, 2018 - Genetic testing pushed for hereditary high cholesterol disease
August 14, 2018 - Researchers discover new genes involved in Alzheimer’s Disease
August 14, 2018 - Medicare to overhaul ACOs but critics fear fewer participants
August 14, 2018 - Adolescent health projects receive meager percentage of global funding, study finds
August 14, 2018 - University Hospitals Seidman Cancer Center launches new CAR-T therapy trial
August 14, 2018 - In the addiction battle, is forced rehab the solution?
August 14, 2018 - Busting myths about milk – Scope
August 14, 2018 - Platelet-rich plasma does not enhance cartilage formation capabilities of stem cells
August 14, 2018 - Wearable devices and ‘mhealth’ technology emerge as promising tools for better health
August 14, 2018 - Johns Hopkins expert panel develops first set of operation-specific opioid prescribing guidelines
August 14, 2018 - Clinical study suggests new treatment direction for head and neck cancer in heavy smokers
August 14, 2018 - Phase 2 Clinical Data Published Showing Summit’s Ridinilazole Preserved Gut Microbiome of Patients with CDI
August 14, 2018 - Cardiac progenitor cells undergo a cell fate switch to build coronary arteries
August 14, 2018 - Study identifies potential guidance to treat gastric cancer patients
August 14, 2018 - Revealed: The molecular mechanism underlying hypertrophic cardiomyopathy, or “workaholic heart”
August 14, 2018 - Diabetes epidemic in Guatemala driven by aging, not obesity
August 14, 2018 - New technology shows potential to streamline the analysis of proteins
August 14, 2018 - Rethinking the stroke rule ‘time is brain’
August 14, 2018 - Incidence of coronary artery compression in children may be more common than previously thought
August 14, 2018 - Study helps to better understand disease caused by Alpha-1 antitrypsin deficiency
August 14, 2018 - AI platform identifies acute neurological illnesses faster than human diagnosis
August 14, 2018 - American College of Rheumatology receives grants to support development of lupus clinical trials
August 14, 2018 - New study explains why women get more migraines than men
August 14, 2018 - American Heart Association Urges Screen Time Limits for Youth
August 14, 2018 - Brief interventions during routine care reduce alcohol use among men with HIV
August 14, 2018 - New genome analysis could identify people at higher risk of common deadly diseases
August 14, 2018 - NIH grant for Mount Sinai to study use of inhaled corticosteroids for treatment of sickle cell disease
August 14, 2018 - Daicel supplies free nanodiamond samples to international researchers
August 14, 2018 - Switching anti-psychotic drugs in first-episode schizophrenia patients does not improve clinical outcomes
August 14, 2018 - Study to examine whether modulating gut bacteria can improve cardiac function in heart failure patients
August 14, 2018 - AI technology could hold key to improving health services
August 14, 2018 - One out of two children not getting enough nutrients needed for their health
August 14, 2018 - Mono-antiplatelet therapy after aortic heart valve replacements may work as well as two drugs
August 14, 2018 - Aid-in-dying patient chooses his last day
August 14, 2018 - Exercise Really Can Chase Away the Blues, to a Point
Investigators eye new target for treating movement disorders

Investigators eye new target for treating movement disorders

image_pdfDownload PDFimage_print

Blocking a nerve-cell receptor in part of the brain that coordinates movement could improve the treatment of Parkinson’s disease, dyskinesia and other movement disorders, researchers at Vanderbilt University have reported.

Their findings, published recently in the journal Neuron, focus on M4, a subtype of the muscarinic acetylcholine family of nerve cell (neuron) receptors activated by binding the neurotransmitter acetylcholine.

The Vanderbilt scientists found that M4 neurons project into the substantia nigra pars reticulata, a small structure near the base of the brain important in regulating movement. Here M4 receptor activation opposes signaling by another class of receptors that binds the neurotransmitter dopamine.

When, in Parkinson’s disease, dopamine-producing neurons begin to die off, the opposing action of M4 neurons can suppress dopamine signaling even further.

Drugs called M4 selective antagonists, which selectively block the M4 receptor, thus may relieve symptoms of the disease.

“M4 muscarinic receptor activation has a much more pivotal role in controlling dopamine signaling than we thought,” said the paper’s corresponding author, P. Jeffrey Conn, Ph.D.

This finding “gives much greater strength to the notion that we could use M4 selective antagonists to treat Parkinson’s disease,” he said.

Drugs that block muscarinic acetylcholine receptors can relieve symptoms of Parkinson’s disease including tremors and muscle rigidity. But because they block the whole muscarinic acetylcholine family of receptors, these drugs cause adverse side effects patients can’t tolerate, said Conn, who directs the Vanderbilt Center for Neuroscience Drug Discovery.

For years L-DOPA, a precursor to dopamine that can replenish the brain’s supply of the neurotransmitter, has been the main treatment for Parkinson’s disease. But L-DOPA is not without its side effects, either.

The identification of different subtypes of the muscarinic acetylcholine receptor raised the possibility of selectively targeting treatment in a way that avoids unwanted side effects.

Conn and his colleagues have been developing potential drugs called positive allosteric modulators that can boost the activity of the M4 receptor like the dimmer in an electrical circuit.

“In schizophrenia there’s excessive dopamine transmission,” he said. “We’ve studying M4 as a way to dampen dopamine function in schizophrenia patients. It’s actually those studies that led us to develop these insights into M4 regulation of dopamine signaling” in movement disorders.

“We used genetic approaches and now have very selective compounds that have anti-parkinsonian activity in animal models,” said Conn, the Lee E. Limbird Professor of Pharmacology in the School of Medicine.

“We’ve shown that with the first one. Now we have much better compounds that we’re going to follow.”


Explore further:
Researchers eye potential schizophrenia ‘switch’

Journal reference:
Neuron

Provided by:
Vanderbilt University

Tagged with:

About author

Related Articles