Tag Archives: Parkinson’s

Parkinson’s, Cancer, and Type 2 Diabetes Share a Key Element That Drives Disease

Parkin protein (green signal) is in a different part of the cell than the mitochondria (red signal) at time 0 (left image) but then co-localizes with the mitochondria after 60 minutes (right image). Credit: Salk Institute

Enzyme with central role in cancer and type 2 diabetes also activates “clean-up” protein in Parkinson’s.

When cells are stressed, chemical alarms go off, setting in motion a flurry of activity that protects the cell’s most important players. During the rush, a protein called Parkin hurries to protect the mitochondria, the power stations that generate energy for the cell. Now Salk researchers have discovered a direct link between a master sensor of cell stress and Parkin itself. The same pathway is also tied to type 2 diabetes and cancer, which could open a new avenue for treating all three diseases.

“Our findings represent the earliest step in Parkin’s alarm response that anyone’s ever found by a long shot. All the other known biochemical events happen at one hour; we’ve now found something that happens within five minutes,” says Professor Reuben Shaw, director of the NCI-designated Salk Cancer Center and senior author of the new work, detailed in Science Advances on April 7, 2021. “Decoding this major step in the way cells dispose of defective mitochondria has implications for a number of diseases.”

Parkin’s job is to clear away mitochondria that have been damaged by cellular stress so that new ones can take their place, a process called mitophagy. However, Parkin is mutated in familial Parkinson’s disease, making the protein unable to clear away damaged mitochondria. While scientists have known for some time that Parkin somehow senses mitochondrial stress and initiates the process of mitophagy, no one understood exactly how Parkin was first sensing problems with the mitochondria—Parkin somehow knew to migrate to the mitochondria after mitochondrial damage, but there was no known signal to Parkin until after it arrived there.

Shaw’s lab, which is well known for their work in the fields of metabolism and cancer, spent years intensely researching how the cell regulates a more general process of cellular cleaning and recycling called autophagy. About ten years ago, they discovered that an enzyme called AMPK, which is highly sensitive to cellular stress of many kinds, including mitochondrial damage, controls autophagy by activating an enzyme called ULK1.

Following that discovery, Shaw and graduate student Portia Lombardo began searching for autophagy-related proteins directly activated by ULK1. They screened about 50 different proteins, expecting about 10 percent to fit. They were shocked when Parkin topped the list. Biochemical pathways are usually very convoluted, involving up to 50 participants, each activating the next. Finding that a process as important as mitophagy is initiated by only three participants—first AMPK, then ULK1, then Parkin—was so surprising that Shaw could scarcely believe it.

To confirm the findings were correct, the team used mass spectrometry to reveal precisely where ULK1 was attaching a phosphate group to Parkin. They found that it landed in a new region other researchers had recently found to be critical for Parkin activation but hadn’t known why. A postdoctoral fellow in Shaw’s lab, Chien-Min Hung, then did precise biochemical studies to prove each aspect of the timeline and delineated which proteins were doing what, and where. Shaw’s research now begins to explain this key first step in Parkin activation, which Shaw hypothesizes may serve as a “heads-up” signal from AMPK down the chain of command through ULK1 to Parkin to go check out the mitochondria after a first wave of incoming damage, and, if necessary, trigger destruction of those mitochondria that are too gravely damaged to regain function.

The findings have wide-ranging implications. AMPK, the central sensor of the cell’s metabolism, is itself activated by a tumor suppressor protein called LKB1 that is involved in a number of cancers, as established by Shaw in prior work, and it is activated by a type 2 diabetes drug called metformin. Meanwhile, numerous studies show that diabetes patients taking metformin exhibit lower risks of both cancer and aging comorbidities. Indeed, metformin is currently being pursued as one of the first ever “anti-aging” therapeutics in clinical trials.

“The big takeaway for me is that metabolism and changes in the health of your mitochondria are critical in cancer, they’re critical in diabetes, and they’re critical in neurodegenerative diseases,” says Shaw, who holds the William R. Brody Chair. “Our finding says that a diabetes drug that activates AMPK, which we previously showed can suppress cancer, may also help restore function in patients with neurodegenerative disease. That’s because the general mechanisms that underpin the health of the cells in our bodies are way more integrated than anyone could have ever imagined.”

Reference: “AMPK/ULK1-mediated phosphorylation of Parkin ACT domain mediates an early step in mitophagy” by Chien-Min Hung, Portia S. Lombardo, Nazma Malik, Sonja N. Brun, Kristina Hellberg, Jeanine L. Van Nostrand, Daniel Garcia, Joshua Baumgart, Ken Diffenderfer, John M. Asara and Reuben J. Shaw, 7 April 2021, Science Advances.
DOI: 10.1126/sciadv.abg4544

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This post originally posted here The European Times News

Parkinson’s disease: Facial masking an early warning sign – four body parts affected

Parkinson’s disease is a progressive condition whereby the signals communicated between the brain and nervous system are disrupted. This causes a number of impairments, many of which relate to movement. The symptoms are often subtle at first but become quite pronounced as the condition advances. Occasionally there may be early warning signs of the condition not found in movement but in a condition known as facial masking. What is it?

When we think of muscles that can be affected by stiffness and slowness, the muscles people work out in the gym are probably the first to come to mind: legs, arms, maybe even abdominals.

But the same stiffness and slowness that can impact your walking and other activities can have more subtle impacts, as well.

One of these is reduced facial expression, also called hypomimia or facial masking, said the Parkinson’s Foundation.

The health site added: “When the muscles of the face are stiff or take longer to move, it can be hard to crack a smile, raise your eyebrows or otherwise express your feelings using your face, which is an important part of how we communicate.

“People might assume you’re upset or depressed all the time, which can be frustrating.”

Other symptoms of Parkinson’s disease include:

  • Tremors
  • Slowed movement (bradykinesia)
  • Rigid muscles
  • Impaired posture and balance
  • Loss of automatic movements
  • Speech changes
  • Writing changes

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This post originally appeared on Daily Express :: Health Feed
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Parkinson’s disease: Six early signs that can alert you to the brain condition – 'smell'

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This post originally appeared on Daily Express :: Health Feed

“A myriad of animal studies document a direct, favourable effect of aerobic-type exercise on the brain,” states an article published in the journal Mayo Clinic Proceedings.

“Some other research has shown that people who consume caffeine — which is found in coffee, tea and cola — get Parkinson’s disease less often than those who don’t drink it,” reports the Mayo Clinic.

According to the health body, green tea is also related to a reduced risk of developing Parkinson’s disease.

However, as it points out, it is still not known whether caffeine actually protects against getting Parkinson’s, or is related in some other way.

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Parkinson’s disease: Four signs that could indicate your risk of developing the condition

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This post originally appeared on Daily Express :: Health Feed

Parkinson’s disease is a progressive condition whereby the signals communicated between the brain and nervous system are disrupted. This causes a number of impairments, many of which relate to movement. The symptoms are often subtle at first but become quite pronounced as the condition advances. What are four early signs you may be at risk?

Poor balance

Parkinson’s specifically targets nerve cells which reside deep within the brain. Basal ganglia nerves control balance and flexibility, so any damage to these nerves can impair a person’s balance.

Your GP will perform a test known as the pull test to assess a person’s balance and determine if it might be Parkinson’s disease.

If you think you may have Parkinson’s, you should speak to your GP.

They can refer you to a Parkinson’s specialist if they think your symptoms need further investigation.

Parkinson’s should only be diagnosed after having a consultation with a specialist.

It’s not always easy to diagnose the condition.

So it’s important that you see a Parkinson’s specialist to get an accurate diagnosis and to consider the best treatment options.

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Parkinson’s disease: The five early symptoms of the degenerative brain disorder

Postural instability

This symptom usually occurs in the later stages of the disease and is a balancing issue.

A person may find it difficult to maintain an upright position and is unstable when standing.

This instability leads to a person with Parkinson’s to often fall over.

Freezing

This is when a person feels as if their feet are glued to the ground, especially when turning or changing direction.

Freezing is also when a person feels like their lower half is stuck but the top half is able to move.

Freezing also affects activities such as speaking or when doing a repetitive movement such as writing.