Health Research

Research identifies RNA structures linked to Parkinson’s

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G-quadruplex (G4) RNA structures promote Ī±-synuclein aggregation, a factor in Parkinson’s

HQ Team

November 20, 2024: A team of researchers from Kumamoto University has found that unique RNA structures known as G-quadruplexes (G4s) facilitate the harmful aggregation of Ī±-synuclein, a key protein implicated in neurodegenerative diseases, particularly Parkinson’s disease.

Understanding Parkinson’s Disease

Parkinson’s disease (PD) affects approximately 6.1 million individuals globally.

The disease is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra (found in the mid brain), leading to a deficiency of dopamine, which manifests in clinical symptoms such as resting tremors, slowness of movement, rigidity, and postural instability

The hallmark of Parkinson’s pathology is the accumulation of Ī±-synuclein protein into aggregates called Lewy bodies, which disrupt neuronal function and contribute to cell death. While the exact cause of Parkinson’s remains unclear, genetic mutations and environmental factors are believed to play significant roles. Age is a substantial risk factor, with projections suggesting that by 2030, the prevalence of PD could increase by over 50% due to the aging population and extended life expectancy

Role of G-Quadruplexes

In healthy neurons, Ī±-synuclein regulates various functions; however, under stress conditionsā€”often marked by elevated calcium levelsā€”it tends to misfold and aggregate. G4s have been shown to interact with other proteins involved in neurodegeneration, such as tau. Research indicates that tau can accelerate Ī±-synuclein aggregation, suggesting a complex interplay between these proteins that may be mediated by G4 structures.Ā This interaction can enhance the toxicity and spread of neurodegenerative pathology

The Kumamoto University researchers led by Professor Norifumi Shioda and Associate Professor Yasushi Yabuki found that G4s act as scaffolds that attract Ī±-synuclein, promoting its aggregation into toxic forms. This discovery highlights G4s as potential targets for therapeutic intervention.

Promising treatment approach

The research team demonstrated that administering 5-ALA, a compound known to inhibit G4 formation, effectively prevented Ī±-synuclein aggregation in model mice exhibiting Parkinsonā€™s-like symptoms.

Remarkably, this treatment not only halted the progression of motor symptoms but also opened a new avenue for early intervention strategies in neurodegenerative diseases.

Broader implications

Given that G4s are also implicated in other neurodegenerative conditions such as Alzheimer’s disease, this discovery could have far-reaching implications for developing treatments across multiple disorders. By targeting G4 regulation, researchers may pave the way for innovative therapies aimed at improving the quality of life for aging populations affected by neurodegeneration.

By focusing on G4s and their role in Ī±-synuclein aggregation, scientists are one step closer to developing effective preemptive strategies against these debilitating conditions.

The study isĀ publishedĀ in the journalĀ Cell.