Researchers have discovered one of the factors behind nerve cell death in Parkinson's disease, unlocking the potential for treatment to slow the progression of this fatal neurodegenerative disorder.
They found that cardiolipin, a molecule inside nerve cells, helps ensure that a protein called alpha-synuclein folds properly. Misfolding of this protein leads to protein deposits that are the hallmark of Parkinson's disease.
These deposits are toxic to nerve cells that control voluntary movement. When too many of these deposits accumulate, nerve cells die.
"Identifying the crucial role cardiolipin plays in keeping these proteins functional means cardiolipin may represent a new target for development of therapies against Parkinson's disease," said the senior author. "Currently there are no treatments that stop nerve cells from dying."
Published in the journal Nature Communications, the study used stem cells collected from people with the disease. The research team studied how nerve cells try to cope with misfolded alpha-synuclein.
"We thought if we can better understand how cells normally fold alpha-synuclein, we may be able to exploit that process to dissolve these aggregates and slow the spread of the disease," senior author said.
The study revealed that, inside cells, alpha-synuclein binds to mitochondrial membrane, where cardiolipin resides. Cells use mitochondria to generate energy and drive metabolism. Authors show in stem cells that α-syn -mutant neurons display fragmented mitochondria and accumulate α-syn deposits that cluster to mitochondrial membranes in response to exposure of cardiolipin on the mitochondrial surface,
Normally, cardiolipin in mitochondria pulls synuclein out of toxic protein deposits and refolds it into a non-toxic shape. Prolonged cardiolipin exposure in α-syn -mutants initiates recruitment of LC3 to the mitochondria and mitophagy. The researchers found that, in people with Parkinson's disease, this process is overwhelmed over time and mitochondria are ultimately destroyed, said the senior author.
"As a result, the cells slowly die. Based on this finding, we now have a better understanding of why nerve cells die in Parkinson's disease and how we might be able to intervene."
Authors also show that co-culture of SNCA-mutant neurons with their isogenic controls results in transmission of α-syn pathology coincident with mitochondrial pathology in control neurons.
https://www.nature.com/articles/s41467-018-03241-9
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
How brain uses bodily signals to regulate fear
Read more
Separating fact from fiction for "anti-aging" diets
Read more
The link between vitamin D and inflammation
Read more
Chronic stress and depression related protein crystallized!
Read more
Thousands of novel brain-expressed gene isoforms identified!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar