Showing posts with label neurodegenerative. Show all posts
Showing posts with label neurodegenerative. Show all posts

Wednesday, June 21, 2017

Progress on Parkinson's

Parkinson's is partly an autoimmune disease, study finds

First direct evidence that abnormal protein in Parkinson's disease triggers immune response

Date:
June 21, 2017
Source:
Columbia University Medical Center
Summary:
Researchers have found the first direct evidence that autoimmunity plays a role in Parkinson's disease, suggesting that immunosuppressants might play a role in treatment.

Autoimmunity plays a role in Parkinson's disease, according to new research.
Credit: © Feng Yu / Fotolia

Researchers have found the first direct evidence that autoimmunity -- in which the immune system attacks the body's own tissues -- plays a role in Parkinson's disease, the neurodegenerative movement disorder. The findings raise the possibility that the death of neurons in Parkinson's could be prevented by therapies that dampen the immune response.

The study, led by scientists at Columbia University Medical Center (CUMC) and the La Jolla Institute for Allergy and Immunology, was published today in Nature.

"The findings raise the possibility that the death of neurons in Parkinson's could be prevented by therapies that dampen the immune response."

"The idea that a malfunctioning immune system contributes to Parkinson's dates back almost 100 years," said study co-leader David Sulzer, PhD, professor of neurobiology (in psychiatry, neurology and pharmacology) at CUMC. "But until now, no one has been able to connect the dots. Our findings show that two fragments of alpha-synuclein, a protein that accumulates in the brain cells of people with Parkinson's, can activate the T cells involved in autoimmune attacks.

"It remains to be seen whether the immune response to alpha-synuclein is an initial cause of Parkinson's, or if it contributes to neuronal death and worsening symptoms after the onset of the disease," said study co-leader Alessandro Sette, Dr. Biol. Sci., professor in the Center for Infectious Disease at La Jolla Institute for Allergy and Immunology in La Jolla, Calif. "These findings, however, could provide a much-needed diagnostic test for Parkinson's disease, and could help us to identify individuals at risk or in the early stages of the disease."

Scientists once thought that neurons were protected from autoimmune attacks. However, in a 2014 study, Dr. Sulzer's lab demonstrated that dopamine neurons (those affected by Parkinson's disease) are vulnerable because they have proteins on the cell surface that help the immune system recognize foreign substances. As a result, they concluded, T cells had the potential to mistake neurons damaged by Parkinson's disease for foreign invaders.

The new study found that T cells can be tricked into thinking dopamine neurons are foreign by the buildup of damaged alpha-synuclein proteins, a key feature of Parkinson's disease. "In most cases of Parkinson's, dopamine neurons become filled with structures called Lewy bodies, which are primarily composed of a misfolded form of alpha-synuclein," said Dr. Sulzer.

The Sulzer and Sette labs are now analyzing these responses in additional patients, and are working to identify the molecular steps that lead to the autoimmune response in animal and cellular models.
"Our findings raise the possibility that an immunotherapy approach could be used to increase the immune system's tolerance for alpha-synuclein, which could help to ameliorate or prevent worsening symptoms in Parkinson's disease patients," said Dr. Sette.

Story Source:
Materials provided by Columbia University Medical Center.


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Thursday, May 25, 2017

Alzheimer's, Parkinson's, and Huntington's diseases share common, crucial feature


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Alzheimer's, Parkinson's, and Huntington's diseases share common crucial feature

Finding suggests that treatment for one disease could work for the other two

Date:
May 23, 2017
Source:
Loyola University Health System
Summary:
A study has found that abnormal proteins found in Alzheimer's, Parkinson's and Huntington's diseases share a similar ability to cause damage when they invade brain cells. The finding suggests that an effective treatment for one neurodegenerative disease might work for other neurodegenerative diseases as well.
FULL STORY

A Loyola University Chicago study has found that abnormal proteins found in Alzheimer's disease, Parkinson's disease, and Huntington's disease all share a similar ability to cause damage when they invade brain cells.

The finding potentially could explain the mechanism by which Alzheimer's, Parkinson's, Huntington's, and other neurodegenerative diseases spread within the brain and disrupt normal brain functions.

The finding also suggests that an effective treatment for one neurodegenerative disease might work for other neurodegenerative diseases as well.

The study by senior author Edward Campbell, PhD, first author William Flavin, PhD, and colleagues is published in the journal Acta Neuropathologica.

"A possible therapy would involve boosting a brain cell's ability to degrade a clump of proteins and damaged vesicles," Campbell said. "If we could do this in one disease, it's a good bet the therapy would be effective in the other two diseases."

Neurodegenerative diseases are caused by the death of neurons and other cells in the brain, with different diseases affecting different regions of the brain. Alzheimer's destroys memory, while Parkinson's and Huntington's affect movement. All three diseases are progressive, debilitating and incurable.

Previous research has suggested that in all three diseases, proteins that are folded abnormally form clumps inside brain cells. These clumps spread from cell to cell, eventually leading to cell deaths. Different proteins are implicated in each disease: tau in Alzheimer's, alpha-synuclein in Parkinson's and huntingtin in Huntington's disease.

The Loyola study focused on how these misfolded protein clumps invade a healthy brain cell. The authors observed that once proteins get inside the cell, they enter vesicles (small compartments that are encased in membranes). The proteins damage or rupture the vesicle membranes, allowing the proteins to then invade the cytoplasm and cause additional dysfunction. (The cytoplasm is the part of the cell that's outside the nucleus).

The Loyola study also showed how a cell responds when protein clumps invade vesicles: The cell gathers the ruptured vesicles and protein clumps together so the vesicles and proteins can be destroyed. However, the proteins are resistant to degradation. "The cell's attempt to degrade the proteins is somewhat like a stomach trying to digest a clump of nails," Campbell said.

Flavin said the finding that protein clumps associated with the three diseases cause the same type of vesicle damage was unexpected. Loyola researchers initially focused on alpha-synuclein proteins associated with Parkinson's disease. So they asked collaborator Ronald Melki, PhD, to send them samples of different types of alpha-synuclein. (To do the experiment in a blinded, unbiased manner, the Loyola researchers did not know which types of alpha-synuclein were which.) Melki, a protein researcher at the Paris-Saclay Institute of Neuroscience, is known for his ability to generate distinct types of alpha-synuclein. Without telling the Loyola researchers, Melki sent other types of proteins as well. This led to the surprise finding that tau and huntingtin proteins also can damage vesicles.

Campbell stressed the study's findings need to be followed up and confirmed in future studies.
The Loyola study is titled, "Endocytic vesicle rupture is a conserved mechanism of cellular invasion by amyloid proteins." It was supported by grants from the Michael J. Fox Foundation, Parkinson's Disease Foundation, Illinois chapter of the ARCS Foundation, Arthur J. Schmitt Foundation and other sources.

Campbell is an associate professor in the Department of Microbiology and Immunology at Loyola University Chicago Stritch School of Medicine. Flavin is a Loyola University Chicago MD/PhD student. Other co-authors are Zachary Green, Stratos Skarpathiotis, and Michael Chaney of Loyola University Chicago; Luc Bousset and Ronald Melki of the Paris-Saclay Institute of Neuroscience; and Yaping Chu and Jeffrey Kordower of Rush University Medical Center.

Story Source:
Materials provided by Loyola University Health System.


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