Summary: Researchers have discovered novel RNA structures known as G-quadruplexes ( G4s ), which promote harmful -synuclein protein aggregation in Parkinson’s disease. Elevated potassium levels trigger these G4s, acting as “scaffolds” for α-synuclein blending. Using 5-aminolevulinic acid (5-ALA ) to model mice resulted in less motor symptoms and aggregation.
This discovery points to the potential for early treatment for degenerative diseases in G4-targeted solutions. The results may also qualify to other situations involving protein formation, such as Alzheimer’s, expanding the potential effects of these remedies. Overall, the study marks a big step forward in neurological studies and therapeutic growth.
Important Information:
- G-quadruplex ( G4 ) RNA structures promote α-synuclein aggregation, a factor in neurodegeneration.
- 5-aminolevulinic acid (5-ALA ) inhibits G4 formation, preventing harmful aggregation.
- The findings point to G4 rules as a possible degenerative disease therapeutic target.
Origin: Kumamoto University
A group of researchers at Kumamoto University has discovered a mechanism that causes harmful proteins aggregates to form, which are responsible for Parkinson’s disease and neurological conditions.
The research team, led by Professor Norifumi Shioda and Associate Professor Yasushi Yabuki, demonstrated for the first time that novel RNA structures called G-quadruplexes ( G4s ) play a significant role in encouraging the aggregation of -synuclein, a protein associated with neurodegeneration.
The research is , published , in the journal , Cell.
By demonstrating that inhibiting G4 council could possibly prevent the onset of influenced, this discovery jobs G4 as a appealing target for , first intervention , in these diseases.
In a good condition, α-synuclein usually regulates cerebral function. But, in , neurological conditions, it particles up, leading to cell destruction and engine symptoms.
The researchers identified that G4s, four-stranded RNA institutions that form in response to , mobile stress, function as a “scaffold” that facilitates α-synuclein formation.
Elevated , potassium levels, frequently seen under pressure, set G4 council, which therefore attracts α-synuclein, converting it into a dangerous, aggregate-prone state.
The staff went a step further, demonstrating a fresh approach to avoid this method. They administered 5-aminolevulinic acid (5-ALA ), a compound that blocks G4 formation, to model mice exhibiting Parkinson ‘s-like symptoms.
Amazingly, 5-ALA treatment not only prevented α-synuclein formation but even halted the development of machine symptoms, a promising sign for possible therapies targeting early-stage aging.
By focusing on G4 legislation, this discovery may make significant strides in neurodegenerative disease treatment. Since G4s are also implicated in various conditions such as Alzheimer’s disease, this identification may enhance the effects of such solutions beyond Parkinson’s disorder.
These findings provide new information on preventive measures to combat neurodegeneration and enhance quality of life for aging populations.
About this genetics and Parkinson’s disease research news
Author: Yasushi Yabuki
Source: Kumamoto University
Contact: Yasushi Yabuki – Kumamoto University
Image: The image is credited to Neuroscience News
Original Research: Open access.
Yasushi Yabuki and colleagues ‘ work” RNA G-quadruplexes form scaffolds that promote neuropathological -synuclein aggregation.” Cell
Abstract
RNA G-quadruplexes create scaffolds that promote the aggregation of neuropathological -synuclein.
Synucleinopathies, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy, are triggered by α-synuclein aggregation, triggering progressive neurodegeneration.
However, the intracellular α-synuclein aggregation mechanism remains unclear.
Herein, we demonstrate that RNA G-quadruplex assembly forms scaffolds for α-synuclein aggregation, contributing to neurodegeneration. Directly through the N terminus, purified RNA binds to RNA G-quadruplexes.
RNA G-quadruplexes undergo Ca2+-induced phase separation and assembly, accelerating α-synuclein sol-gel phase transition.
In α-synuclein preformed fibril-treated neurons, RNA G-quadruplex assembly comprising synaptic mRNAs co-aggregates with α-synuclein upon excess cytoplasmic Ca2+ , influx, eliciting synaptic dysfunction.
Forced RNA G-quadruplex assembly using an optogenetic approach evokes α-synuclein aggregation, causing neuronal dysfunction and neurodegeneration.
The administration of 5-aminolevulinic acid, a protoporphyrin IX prodrug, prevents RNA G-quadruplex phase separation, thereby attenuating α-synuclein aggregation, neurodegeneration, and progressive motor deficits in α-synuclein preformed fibril-injected synucleinopathic mice.
Therefore, Ca2+ , influx-induced RNA G-quadruplex assembly accelerates α-synuclein phase transition and aggregation, potentially contributing to synucleinopathies.
