Breaking News
March 27, 2019 - Managing MS
March 27, 2019 - Researchers reveal how receptor TLR-9 protects against lupus
March 27, 2019 - Doctors share story of daughter’s treatment for leukemia
March 27, 2019 - Medical Center Hosts Networking Session for Women’s History Month
March 27, 2019 - Positive link found between anxiety during childhood, adolescence with later alcohol use disorders
March 27, 2019 - Coronary artery calcium indicates patients’ imminent risk of a heart attack
March 27, 2019 - Luxia Scientific partners with Life Genomics to commercialize microbiome-based tests in the Nordic countries
March 26, 2019 - New mathematical algorithm objectively classifies shapes of neurons in the brain
March 26, 2019 - Research suggests oxytocin as potential new obesity treatment
March 26, 2019 - Education may not protect against dementia as previously thought
March 26, 2019 - Stanford acquires archive of palliative care pioneer Elisabeth Kübler-Ross | News Center
March 26, 2019 - New research aims to turn worms against parasite-associated cancer
March 26, 2019 - Psychological evolution may help explain differences between male and female serial killers
March 26, 2019 - New molecular mechanism involved in pancreas repair identified
March 26, 2019 - Obesity linked to reproductive problems in women with type 1 diabetes
March 26, 2019 - New short-pulse ultrasound technique enhances drug delivery to brains of mice
March 26, 2019 - Researchers uncover mechanism that initiates sexual organs maturation
March 26, 2019 - DermBiont Begins Phase 2 Clinical Trial for Athlete’s Foot with a Live Bacterial Topical Probiotic
March 26, 2019 - Persons with Alzheimer’s disease have a higher risk of head injuries
March 26, 2019 - Mental health issues associated with income inequalities in Indigenous people
March 26, 2019 - Participation in sports linked with fewer depressive symptoms in children
March 26, 2019 - Brain process common to sleep and aging discovered
March 26, 2019 - People under age 50 with hearing loss more likely to misuse alcohol and drugs
March 26, 2019 - People with and without cancer use different dosages of cannabis formulations, study shows
March 26, 2019 - Young people at risk of addiction show differences in key brain region
March 26, 2019 - In virtual exchange, students in California and Lebanon unite to improve refugee health
March 26, 2019 - Trump Administration Changes Course, Asks Court To Strike Down ACA
March 26, 2019 - People with untreated diabetes develop signs of Alzheimer’s disease at a faster rate
March 26, 2019 - Study explains how bright colors evolved and diversified in male guppies
March 26, 2019 - Savings from lower insurance costs of growth hormone drugs not passed on to patients
March 26, 2019 - Study highlights the need to pay more attention on specific nutritional needs of female athletes
March 26, 2019 - Sleep quality varies throughout menstrual cycle in young women
March 26, 2019 - A1c diabetes blood test found to be unreliable
March 26, 2019 - Younger Female Blood Donors Vulnerable to Iron Deficiency
March 26, 2019 - Prostate cancer cells ‘spit out’ a protein that promotes tumor growth
March 26, 2019 - Finding the elusive drinking ‘brake’
March 26, 2019 - Using the Mastermind strategy in brain research
March 26, 2019 - Symptomatic pharmacotherapy of elderly people should be regularly monitored
March 26, 2019 - Synthetic biological logic gate could one day be used to modify cellular function
March 26, 2019 - Damage to anxiety-associated brain region heightens monkeys’ defensive response
March 26, 2019 - Researchers uncover large-scale brain patterns and networks which control sleep
March 26, 2019 - Scientific Symposium at LABVOLUTION focuses on key issues in life sciences
March 26, 2019 - Screen time plus snacking could increase risk for metabolic syndrome in teens
March 26, 2019 - Attention, Seniors: Drink More Water and Head Off Disease
March 26, 2019 - Peptide shows promise for protecting kidneys from nephritis
March 26, 2019 - Causes of diabetes decline or disappear when ‘zombie cells’ are removed, shows study
March 26, 2019 - Scientists identify common genetic variants associated with post-stroke recovery
March 26, 2019 - Study finds link between menopause and changes in body composition
March 26, 2019 - Higher levels of sex hormones in older men related to lower biological age
March 26, 2019 - Research links participation in team sports to larger hippocampal volumes in children
March 26, 2019 - Cerveau announces research collaboration agreement with Eisai for novel tau imaging agent
March 26, 2019 - New technique measures frequency of sounds emitted from biological structures
March 26, 2019 - Removal of ‘zombie cells’ alleviates causes of diabetes in obese mice
March 26, 2019 - Women exposed to deepwater horizon oil spill continue to experience PTSD symptoms
March 26, 2019 - Shaping new treatments for tuberculosis
March 26, 2019 - Understanding genetic interactions holds key to new personalized therapies
March 26, 2019 - Nervous system relies on guidance cues for neuronal axons to reach destinations
March 26, 2019 - Altering gut microbiome may be potential treatment option for PCOS
March 26, 2019 - Moleculin Files with FDA for Expedited Approval Pathway for Annamycin
March 26, 2019 - GPs play pivotal role in ensuring success of new Faster Diagnosis Standard for Cancer
March 26, 2019 - New clues discovered to lung transplant rejection
March 26, 2019 - New study offers insight into development of delusions
March 26, 2019 - Children’s ball pits full of pathogenic microbes
March 26, 2019 - Exploring pathophysiological factors that link sleep problems and Alzheimer’s disease
March 26, 2019 - Walking downhill after meals can reduce bone resorption in postmenopausal women with diabetes
March 26, 2019 - USA LESS Issues Voluntary Nationwide Recall of LEOPARD Miracle Honey Due to Presence of Undeclared Sildenafil
March 26, 2019 - CT scan prior to spine fusion finds almost half of patients had undiagnosed osteoporosis
March 26, 2019 - After 2 Apparent Student Suicides, Parkland Grieves Again
March 25, 2019 - Inherited form of rickets improves more with new injectable medicine than conventional therapy
March 25, 2019 - Trastuzumab Tied to Higher Long-Term Risk for Heart Failure
March 25, 2019 - Personal context directly affects CPAP use
March 25, 2019 - Mosquito tracking key to preventing disease outbreaks
March 25, 2019 - Scientists Detect Hidden Signals from Beneficial Bacteria
March 25, 2019 - Treating women with thyroid antibodies with Levothyroxine do not increase live birth rate
March 25, 2019 - Brain area that only processes spoken, not written words identified
March 25, 2019 - Race and ethnicity influence fracture risk in diabetic patients
March 25, 2019 - Researchers report new regenerative medicine approach for treating osteoarthritis of the knee
March 25, 2019 - Exposure to dim light at night may contribute to spread of breast cancer to bones
March 25, 2019 - Benefits of osteoporosis treatment in postmenopausal women outweigh the perceived risks
March 25, 2019 - Researchers find evidence of Cryptosporidium parasite in Minnesota’s public water systems
New transgenic mouse model sheds light on biological causes of Parkinson’s disease

New transgenic mouse model sheds light on biological causes of Parkinson’s disease

image_pdfDownload PDFimage_print

Parkinson’s disease (PD) is a neurodegenerative disorder that presents clinically with abnormal movement and tremors at rest. In the brain, PD is marked by the accumulation of the protein, α-synuclein (αS), into clumps known as Lewy bodies, which diminish neural health. Previous research suggests abnormal αS can alter cell membrane function and lead to cell death. Investigators from Brigham and Women’s Hospital have developed a unique mouse model to induce PD-like αS aggregation, leading to resting tremor and abnormal movement control. This mouse model responds to L-DOPA, similarly to patients with PD. The research team’s results on the use of this transgenic mouse model appear this week in Neuron.

“It is difficult to find efficient treatment therapies that target αS aggregation,” said lead author Silke Nuber, PhD, an instructor in the Ann Romney Center for Neurologic Diseases at BWH. “Thus, it is necessary to develop mouse models that reflect the long-term changes, including Lewy-like aggregation of αS and an associated close PD-phenotype, to better understand the mechanisms that lead to the initiation of PD.”

In a healthy brain, this lab first reported (Bartels et al, Nature 2011) that αS can occur normally in the form of helically folded tetramers (four units of αS wound around each other), a form that resists the aggregation that abnormal αS monomers undergo. To model the brain in PD, Nuber and her team created a novel transgenic mouse that has a tetramer-lowering mutation, which leads to αS deposits, loss of dopamine and neurotoxicity.

“With these new mice, we set out to examine the upstream role of tetramer-lowering mutations and their relevance to PD,” Nuber said. “Our hypothesis was that upstream destabilization of normal tetramers to excess monomers can lead to the changes of PD.”

To examine the effect of tetramer-abrogating mutations on αS pathology, the research team created multiple mouse lines with certain αS mutations that chronically decrease the tetramers, increase free monomers and lead to neuronal dysfunction and degeneration. They then compared their new tetramer-abrogating mouse to a mouse expressing normal human αS protein and a mouse with just a single familial PD αS mutation. The mice were carefully evaluated side-by-side for key biochemical, histological and behavioral characteristics associated with PD.

The new tetramer-abrogating mouse displayed key PD-like changes, including age-dependent αS aggregation in altered neurons and distinctive abnormal movements. These changes were all derived from preventing normal αS tetramer formation. These findings strongly suggest that tetramers are required for the normal state of αS in the brain. The authors conclude that it is likely that shifting tetramers to monomers can initiate PD. They also note that the phenotype was more prominent in male mice, which is reminiscent to what occurs in PD, a finding they plan to follow up on within the framework of the Women’s Brain Initiative at BWH.

“We can now examine PD in a whole new light. We can think about stabilizing the physiological αS tetramer, an entirely novel therapeutic concept, as a means of preventing or delaying the onset of PD,” said Nuber.

“With our lab’s experience in deciphering the earliest stages of Alzheimer’s disease, we decided some time ago to apply analogous approaches to the different protein abnormality occurring in PD,” said Dennis Selkoe, MD, the senior author of the paper and the co-director of the Ann Romney Center for Neurologic Disease at BWH. “We believe this unique mouse model shows that the tetrameric form of αS we discovered in 2011 is necessary for normal neuronal function, so that abrogating the tetramer has direct PD-like consequences. This PD mouse model will provide a new route to entirely novel therapeutic approaches.”

Source:

https://www.brighamandwomens.org/

Tagged with:

About author

Related Articles