PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

An amyloid link between Parkinson's disease and melanoma

An amyloid link between Parkinson's disease and melanoma
2021-04-07
(Press-News.org) WASHINGTON, April 7, 2021 -- On the surface, Parkinson's disease -- a neurodegenerative disorder -- and melanoma -- a type of skin cancer -- do not appear to have much in common. However, for nearly 50 years, doctors have recognized that Parkinson's disease patients are more likely to develop melanoma than the general population. Now, scientists report a molecular link between the two diseases in the form of protein aggregates known as amyloids.

The researchers will present their results today at the spring meeting of the American Chemical Society (ACS). ACS Spring 2021 is being held online April 5-30. Live sessions will be hosted April 5-16, and on-demand and networking content will continue through April 30. The meeting features nearly 9,000 presentations on a wide range of science topics.

"Several studies have shown that melanoma occurs two to six times more frequently in the Parkinson's population than the healthy population," says Dexter Dean, Ph.D., a postdoctoral fellow at the National Heart, Lung, and Blood Institute (NHLBI), who is presenting the work at the meeting. "What's more, the protein involved in Parkinson's disease, α-synuclein, is elevated in melanoma cells."

In Parkinson's disease, α-synuclein forms amyloid deposits that are thought to kill dopamine-producing neurons in the brain, causing symptoms such as tremor, slow movements and dementia. While intense research has focused on the effects of α-synuclein in the brain, much less is known about its presence or activities in other tissues. However, scientists have evidence that the amyloid-forming protein is expressed more in melanoma cells than in healthy skin. Furthermore, higher levels of α-synuclein in melanocytes (the skin cells that give rise to melanoma) correlate with reduced pigment, or melanin, production. Melanin protects skin from damage by the sun's ultraviolet rays.

Jennifer Lee, Ph.D., Dean's postdoctoral advisor at NHLBI, part of the National Institutes of Health, had previously studied another amyloid-forming protein called premelanosomal protein (Pmel). "Most people know that amyloids are involved in diseases, such as Parkinson's and Alzheimer's, but it's less well-known that some amyloids, like Pmel, actually serve a useful function," Lee says. In healthy melanocytes, Pmel forms amyloid fibrils that act as scaffolds to store melanin in melanosomes (the organelle where the pigment is produced, stored and transported). "Because both α-synuclein and Pmel are expressed in melanoma cells, we wondered if these two amyloid proteins could interact, and whether this interaction could be relevant to the correlation between Parkinson's disease and melanoma," Lee says.

To investigate whether α-synuclein and Pmel could interact, the researchers used microscopy and western blotting to show that the two proteins both resided in the melanosomes of human melanoma cells. When Dean added preformed α-synuclein amyloid to a test tube containing the amyloid-forming region of Pmel (known as the repeat, or RPT, domain), the α-synuclein fibrils stimulated Pmel to aggregate and form a twisted fibril structure that the protein does not normally adopt on its own.

Because α-synuclein in melanoma cells may also be found in its soluble, or non-amyloid, form, the researchers performed other in vitro experiments in which they added soluble α-synuclein to the Pmel RPT domain. In this case, α-synuclein inhibited Pmel's ability to self-aggregate and form amyloid in a concentration-dependent manner. They traced this activity to the first 60 amino acids of α-synuclein.

"We now have preliminary data that suggest an amyloid from one protein can 'seed' or template amyloid from another, and in the soluble form, α-synuclein prevents Pmel aggregation." Lee says. "Therefore, we think that both forms of α-synuclein could diminish melanin biosynthesis -- the amyloid form by causing Pmel to form an unusual twisted structure, and the soluble form by stopping Pmel from aggregating like it should." Loss of skin pigmentation could contribute to the increased melanoma risk in Parkinson's disease patients, the researchers say.

"I think we're just at the tip of the iceberg of appreciating what α-synuclein might be doing in melanoma," Dean says. "In future experiments, I'm really interested in understanding more about what α-synuclein is doing to promote melanoma proliferation, in addition to this interaction with Pmel."

INFORMATION:

A press conference on this topic will be held Wednesday, April 7, at 11 a.m. Eastern time online at http://www.acs.org/acsspring2021conferences.

The researchers acknowledge funding from the National Institutes of Health Intramural Research Program.

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS' mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and its people. The Society is a global leader in providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a specialist in scientific information solutions (including SciFinder® and STN®), its CAS division powers global research, discovery and innovation. ACS' main offices are in Washington, D.C., and Columbus, Ohio.   To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

Note to journalists: Please report that this research was presented at a meeting of the American Chemical Society.   Follow us: Twitter | Facebook

Title Defining an amyloid link between Parkinson's disease and melanoma

Abstract While Parkinson's disease (PD), a neurodegenerative disorder leading to cell death, and melanoma, a cancer of melanocytes leading to uncontrolled cell growth, fundamentally differ, a unique connection between the two diseases has been observed for nearly 50 years. Epidemiological studies have shown that melanoma occurs 2-6 times more frequently in PD patients as compared to the general population, and that individuals with melanoma are more susceptible to PD. α-Synuclein (α-syn), the hallmark pathological protein observed in Lewy bodies from brains of PD patients, is elevated in melanoma, suggesting that α-syn could be a molecular link between the two diseases. A consistent observation is that α-syn expression is inversely correlated to the amount of pigment or melanin found in melanoma cells. Currently, little is known about the role that α-syn plays in melanoma progression. We propose a novel hypothesis that there is an amyloid link between α-syn and Pmel (pre-melanosomal protein), a functional amyloid that promotes melanin biosynthesis in melanocytes. Using confocal immunofluorescence microscopy and western blotting of SK-MEL 28 human melanoma cells, we recently reported that endogenous α-syn and Pmel compartmentalize within the melanosome, the organelle in which melanin is synthesized, and that α-syn fibrils stimulate the aggregation of Pmel repeat domain (RPT) in vitro. Here, we further define this interaction by showing that soluble (disordered) α-syn acts as an inhibitor of RPT aggregation in a concentration-dependent manner, with an estimated half maximum inhibition (IC50) of 200 nM. Using two different truncated α-syn constructs spanning N- and C-terminal residues, 1-60 and 66-140, we show that the amphipathic N-terminus of α-syn alone can inhibit RPT aggregation, while the latter half has no impact. Taken together, these results support our hypothesis that α-syn, a pathogenic amyloid, infiltrates and disrupts conventional Pmel amyloid formation, thus leading to the modulation of melanin production, the biological function of Pmel.


[Attachments] See images for this press release:
An amyloid link between Parkinson's disease and melanoma

ELSE PRESS RELEASES FROM THIS DATE:

Comfort care beneficial for hospitalized stroke patients, yet disparities in use persist

2021-04-07
DALLAS, April 7, 2021 — Receiving palliative or hospice care services was found to improve quality of life for hospitalized ischemic stroke patients, however, disparities persist in which patients are prescribed or have access to these holistic comfort care options, according to new research published today in the Journal of the American Heart Association, an open access journal of the American Heart Association. Prior to the COVID-19 pandemic, stroke ranked No. 5 among all causes of death in the U.S. Nearly 9 in 10 strokes are ischemic strokes caused by a blockage in a blood vessel that carries blood to the brain. Despite advances in acute stroke treatment and management, stroke remains a leading cause of serious long-term disability in the U.S. “Stroke ...

Skoltech scientists create a new electronegativity scale

2021-04-07
Skoltech chemists have proposed a new electronegativity scale and published their findings in Nature Communications. The concept of electronegativity introduced by Linus Pauling, a great American chemist, in the 1930s refers to the ability of an atom to attract electron density. In a chemical bond, the more electronegative atom gains extra electrons, becoming negatively charged, while the less electronegative one loses electrons and becomes positively charged. Electronegativity is a fundamental notion, essential for explaining things that range from chemical bonds' energy to the (in)stability of chemical compounds and the color and hardness of crystals. Since then, chemists have come up with various definitions and scales of electronegativity. Yet Pauling's ...

The future of biodiversity collections

2021-04-07
Events such as the COVID-19 pandemic have highlighted the crucial role played by biodiversity collections in enabling rapid responses to crises and in facilitating ongoing research across numerous fields. Despite the recognized value of this infrastructure, the community nevertheless has further opportunities to maximize its value to the scientific enterprise. Writing in BioScience, Barbara Thiers of the New York Botanical Garden and colleagues describe (https://academic.oup.com/bioscience/article-lookup/doi/10.1093/biosci/biab036) the necessary steps for the biodiversity collections community to vouchsafe its position as an important catalyst of research. The authors draw on recommendations ...

We don't know how most mammals will respond to climate change, warn scientists

2021-04-07
A new scientific review has found there are significant gaps in our knowledge of how mammal populations are responding to climate change, particularly in regions most sensitive to climate change. The findings are published in the British Ecological Society's Journal of Animal Ecology. Nearly 25% of mammal species are threatened with extinction, with this risk exacerbated by climate change. But the ways climate change is impacting animals now, and projected to in the future, is known to be complex. Different environmental changes have multiple and potentially contrasting, ...

Family child care home providers with high diet self-efficacy are better equipped to manage stress

2021-04-07
Philadelphia, April 7, 2021 - Building family child care home providers' (FCCH) self-efficacy--an individual's belief in their ability to manage their situation--for healthy eating is an important component of health promotion and can buffer the impact of stress on their diet quality, according to a new study in the Journal of Nutrition Education and Behavior, published by Elsevier. "The FCCH provider is an important source of child care in this country. A lot of families from lower-income environments use the FCCH because of its affordability and location," said Dianne Ward, EdD, of the Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. FCCH providers can experience multiple stressors ...

Poor children are 'failed by system' on road to higher education in lower-income countries

2021-04-07
A generation of talented but disadvantaged children are being denied access to higher education because academic success in lower and middle-income countries is continually 'protected by wealth', a study has found. The research, which used data from around 3,500 young people in Ethiopia, India, Peru and Vietnam, shows that promising but poorer students 'fall away' during their school years, as challenges associated with their socio-economic circumstances gradually erode their potential. Among children who showed similar levels of ability aged 8, for example, the wealthiest were often over 30 percentage points more likely than the least-wealthy to enter all forms of tertiary education: including university, technical colleges, and teacher training. Even ...

Are early treatments for cerebral palsy effective?

2021-04-07
Symptoms of cerebral palsy, a neurological disorder that affects a person's ability to move and maintain balance and posture, appear early during childhood. A new analysis examines the effectiveness of therapies initiated from birth until 3 years of age for children with or at risk for cerebral palsy. The analysis, which is published in Developmental Medicine & Child Neurology, included all systematic reviews from 2009-2020 that assessed the results of relevant published studies. Investigators concluded that research has generated limited supportive data and cannot yet confirm a greater benefit from early versus later interventions; however, earlier, ...

Program may help patients with rheumatic diseases quit smoking

2021-04-07
Smoking increases symptoms and health risks for patients with rheumatic diseases, but interventions to help patients quit are rarely available at rheumatology clinics. A study published in Arthritis Care & Research has found that Quit Connect--a protocol involving electronic health record prompts for nurses and medical assistants in rheumatology clinics--can increase electronic referrals to free, state-run tobacco quite lines. Implementing Quit Connect led to electronic referrals for 71% of patients who were identified as ready to quit, with referrals taking less than 90 seconds for medical staff to complete. "There's a huge opportunity to address smoking as a modifiable risk factor in rheumatology patients, and Quit Connect was 26-times more effective than usual care for ...

Do school-based interventions help improve reading and math in at-risk children?

2021-04-07
School-based interventions that target students with, or at risk of, academic difficulties in kindergarten to grade 6 have positive effects on reading and mathematics, according to an article published in END ...

Study examines ADHD symptoms, stress, and resilience in college students

2021-04-07
In a study of 558 college students, those who reported more symptoms associated with attention-deficit/hyperactivity disorder (ADHD) also reported higher levels of stress. Students reporting higher levels of ADHD symptoms also reported lower levels of resilience, according to the study published in the END ...

LAST 30 PRESS RELEASES:

Storing electrons from hydrogen for clean chemical reactions

Unlocking how to use mRNA to target Alzheimer’s disease

Kessler Foundation secures $770,000 in grants to advance leading-edge spinal cord research

Going ‘back to the future’ to forecast the fate of a dead Florida coral reef

How extratropical ocean-atmosphere interactions can contribute to the variability of jet streams in the Northern Hemisphere

MSK Research Highlights, March 28, 2024

USDA, Nueta Hidatsa Sahnish College collaborate to support Indigenous Seed Sovereignty

For younger women, mental health now may predict heart health later

Missed opportunity: AEDs near cardiac arrests rarely used by bystanders

Eggs may not be bad for your heart after all

Alcohol raises heart disease risk, particularly among women

TTUHSC announces new center for nursing research

Adding just enough fuel to the fire

Impact of synbiotic supplements on the gut microbiome and overall health of penguins

Promising advances in organosilica membranes for separating organic liquid mixtures

Cell phone video technology unveils new method for analyzing walking and gait

Ancient isolation’s impact on modern ecology

Synaptic protein change during development offers clues on evolution and disease

How commercial rooftop solar power could bring affordable clean energy to low-income homes

Taking a closer look at pulmonary fibrosis genetics

Cats with MDR1 mutation at risk of severe reactions to popular medication

IOP Publishing and IPEM mandate reporting of sex and gender in research 

Dogs trained to detect trauma stress by smelling humans’ breath

Electronic device thermal management made simpler and slightly better!

Study: Dangerous surgical site infections can be reduced with simple prevention protocol

Genetic testing of patients with atrial fibrillation can alert clinicians to potential development of life-threatening conditions

Artificial Intelligence tool successfully predicts fatal heart rhythm

What progress has China made in agriculture green development over the past five years?

ALMA finds new molecular signposts in starburst galaxy

Open waste burning linked to air pollution in Northwestern Greenland

[Press-News.org] An amyloid link between Parkinson's disease and melanoma