Breaking News
February 23, 2019 - U.S.-based patient advocacy organizations received majority of pharma donations, finds study
February 23, 2019 - UCL and AIIMS collaborates to increase academic and student exchange
February 23, 2019 - Mechanism behind how diabetes causes muscle loss revealed
February 23, 2019 - Hepatocellular carcinoma diagnosis, prognosis and treatment may improve by identifying a protein
February 23, 2019 - The American Heart Association issues new reference toolkit for healthcare providers
February 23, 2019 - Studies explore physiological dangers that climate change will have on animal life
February 23, 2019 - Penn study reveals increase in health-related internet searches before ER visits
February 23, 2019 - Intensive therapy during early stages of MS leads to better long-term outcomes
February 23, 2019 - Prenatal Fluconazole Exposure Increases Neonatal Risks
February 23, 2019 - Mental Health Screening: MedlinePlus Lab Test Information
February 23, 2019 - Study suggests birth mechanics are part of the process that leads to autism
February 23, 2019 - Unhealthy diet linked to poor mental health
February 23, 2019 - Study gives a snapshot of crocodile evolution
February 23, 2019 - Research finds steep rise in self-poisonings among young people
February 23, 2019 - American Gastroenterological Association announces “AGA Future Leaders Program”
February 23, 2019 - Scientists uncover new mechanisms regulating neural stem cells
February 23, 2019 - Combinations of certain insecticides turn out to be lethal for honeybees
February 23, 2019 - AHA News: Why Are Black Women at Higher Risk of Dying From Pregnancy Complications?
February 23, 2019 - NIMH » Anxiety Disorders
February 23, 2019 - Autistic people urgently need access to tailored mental health support
February 23, 2019 - Newly designed molecule could benefit people with Friedrich’s Ataxia
February 23, 2019 - Chinese CRISPR twins may have better cognition and memory
February 23, 2019 - Study finds new genetic clues associated with asthma in African ancestry populations
February 23, 2019 - Fetal signaling pathways may offer future opportunities to treat lung damage
February 23, 2019 - Early-stage osteoarthritis drug wins prestigious innovation award
February 23, 2019 - Researchers report positive findings with dasotraline for ADHD in children ages 6-12
February 23, 2019 - News study reanalyzes the effects of noncaloric sweeteners on gut microbiota
February 23, 2019 - New device allows scientists to reproduce blow effects on the heart in lab
February 23, 2019 - Holy herb identified as a potential treatment for Alzheimer’s disease
February 23, 2019 - New technology platform digitally counts growth factors in single cells
February 23, 2019 - Physicians still remain at higher risk for burnout compared to other professionals
February 23, 2019 - Surgery and other treatments offer viable options for adult scoliosis
February 23, 2019 - Reduced antibody adaptability may make the elderly more vulnerable to influenza
February 23, 2019 - Researchers find increased rates of CRC screening in Kentucky after Medicaid expansion
February 23, 2019 - Neighborhood income, education associated with risk of disability progression in MS patients
February 23, 2019 - Endocrine Society opposes new rule that restricts access to Title X Family Planning Program
February 23, 2019 - 2019 guidelines for management of patients with atrial fibrillation
February 23, 2019 - Surprise rheumatoid arthritis discovery points to new treatment for joint inflammation
February 23, 2019 - A just-right fix for a tiny heart
February 23, 2019 - UMass Amherst scientist explores role of citrus peel in decreasing gut inflammation
February 23, 2019 - Owlstone Medical and Shanghai Renji Hospital collaborate to initiate breath biopsy lung cancer trial
February 23, 2019 - AMSBIO’s comprehensive portfolio of knock-out cell lines and lysates
February 23, 2019 - New app reliably determines physicians’ skills in forming accurate, efficient diagnoses
February 23, 2019 - Peripheral nerve injury can trigger the onset and spread of ALS, shows study
February 23, 2019 - Researchers uncover mechanisms that prevent tooth replacement in mice
February 23, 2019 - Once-a-day capsule offers new way to reduce symptoms of chronic breathlessness
February 23, 2019 - FDA Adds Boxed Warning for Increased Risk of Death with Gout Medicine Uloric (febuxostat)
February 23, 2019 - Phone-based intervention aids rheumatoid arthritis care
February 23, 2019 - Opioid epidemic makes eastern inroads and targets African-Americans
February 23, 2019 - New identified biomarker predicts patients who might benefit from HER2-targeted agents
February 23, 2019 - Study offers new insights into mechanisms of changes in erythrocytes under stress
February 23, 2019 - Antipsychotic polypharmacy may be beneficial for schizophrenia patients
February 23, 2019 - Researchers investigate how marijuana and tobacco co-use affects quit attempts by smokers
February 23, 2019 - Patients with diabetes mellitus have high risk of stable ischemic heart disease
February 23, 2019 - Transparency on healthcare prices played key role in Arizona health system’s turnaround
February 23, 2019 - A comprehensive, multinational review of peppers around the world
February 23, 2019 - Study finds modest decrease in burnout among physicians
February 23, 2019 - A simple change can drastically reduce unnecessary tests for urinary tract infections
February 23, 2019 - Deep Learning-Enhanced Device Detects Diabetic Retinopathy
February 23, 2019 - Researchers discover new binding partner for amyloid precursor protein
February 23, 2019 - Modest decrease seen in burnout among physicians, researchers say | News Center
February 23, 2019 - Transplanting bone marrow of young mice into old mice prevents cognitive decline
February 23, 2019 - Mogrify to accelerate novel IP and cell therapies using $3.7m USD funding
February 23, 2019 - Johns Hopkins study describes cells that may help speed bone repair
February 23, 2019 - Scientists demonstrate influence of food odors on proteostasis
February 23, 2019 - Researchers unlock the secret behind reproduction of fish called ‘Mary’
February 23, 2019 - Acupuncture Could Help Ease Menopausal Symptoms
February 23, 2019 - Researchers use AI to detect early signs of Alzheimer’s
February 23, 2019 - On recovery, vulnerability and ritual: An exhibit in white | News Center
February 23, 2019 - Memory Stored in Unexpected Region of the Brain
February 23, 2019 - Several health experts worldwide gather at EUDONORGAN event
February 23, 2019 - Discovery of potent compound in native California shrub may lead to treatment for Alzheimer’s
February 22, 2019 - Researchers create new map of the brain’s own immune system
February 22, 2019 - ICHE’s reviews on surgical infections, unnecessary urine tests, and nurses’ role in antibiotic stewardship
February 22, 2019 - UK Research and Innovation invests £200 million to create new generation of AI leaders
February 22, 2019 - Takeda collaboration to boost fight against Alzheimer’s and other neurodegenerative diseases
February 22, 2019 - Heavy drinking may change DNA, leading to increased craving for alcohol
February 22, 2019 - U.S. opioid deaths jump fourfold in 20 years; epidemic shifts to Eastern states | News Center
February 22, 2019 - 5 Questions with William Turner on Diversity in Medicine
February 22, 2019 - HHS Finalizes Rule Seeking To Expel Planned Parenthood From Family Planning Program
Drug homing method helps rethink Parkinson’s

Drug homing method helps rethink Parkinson’s

image_pdfDownload PDFimage_print
Drug homing method helps rethink Parkinson’s
Only cells expressing the HaloTag receptor can bind to the AMPA-repressing drug, ensuring virtually perfect cell-type specificity. Credit: Duke Research Blog

The brain is the body’s most complex organ, and consequently the least understood. In fact, researchers like Michael Tadross, MD, PhD, wonder if the current research methods employed by neuroscientists are telling us as much as we think.

Current methods such as gene editing and pharmacology can reveal how certain genes and drugs affect the cells in a given area of the brain, but they’re limited in that they don’t account for differences among different cell types. With his research, Tadross has tried to target specific cell types to better understand mechanisms that cause neuropsychiatric disorders.

To do this, Tadross developed a method to ensure a drug injected into a region of the brain will only affect specific cell types. Tadross genetically engineered the cell type of interest so that a special receptor protein, called HaloTag, is expressed at the cell membrane. Additionally, the drug of interest is altered so that it is tethered to the molecule that binds with the HaloTag receptor. By connecting the drug to the Halo-Tag ligand, and engineering only the cell type of interest to express the specific Halo-Tag receptor, Tadross effectively limited the cells affected by the drug to just one type. He calls this method “Drugs Acutely Restricted by Tethering,” or DART.

Tadross has been using the DART method to better understand the mechanisms underlying Parkinson’s disease. Parkinson’s is a neurological disease that affects a region of the brain called the striatum, causing tremors, slow movement, and rigid muscles, among other motor deficits.

Patients with Parkinson’s show decreased levels of the neurotransmitter dopamine in the striatum. Consequently, treatments that involve restoring dopamine levels improve symptoms. For these reasons, Parkinson’s has long been regarded as a disease caused by a deficit in dopamine.

With his technique, Tadross is challenging this assumption. In addition to death of dopaminergic neurons, Parkinson’s is associated with an increase of the strength of synapses, or connections, between neurons that express AMPA receptors, which are the most common excitatory receptors in the brain.

In order to simulate the effects of Parkinson’s, Tadross and his team induced the death of dopaminergic neurons in the striatum of mice. As expected, the mice displayed significant motor impairments consistent with Parkinson’s. However, in addition to inducing the death of these neurons, Tadross engineered the AMPA-expressing cells to produce the Halo-Tag protein.

Tadross then treated the mice striatum with a common AMPA receptor blocker tethered to the Halo-Tag ligand. Amazingly, blocking the activity of these AMPA-expressing neurons, even in the absence of the dopaminergic neurons, reversed the effects of Parkinson’s so that the previously affected mice moved normally.

Tadross’s findings with the Parkinson’s mice exemplifies how little we know about cause and effect in the brain. The key to designing effective treatments for neuropsychiatric diseases, and possibly other diseases outside the nervous system, may be in teasing out the relationship of specific types of cells to symptoms and targeting the disease that way.

The ingenious work of researchers like Tadross will undoubtedly help bring us closer to understanding how the brain truly works.


Explore further:
Homing system delivers drugs to specific neurons

Provided by:
Duke Research Blog

Tagged with:

About author

Related Articles