ATP‘s Surprising Role in Neurodegenerative diseases
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BUCHAREST — April 24, 2025 — New research unveils the surprising role of ATP in neurodegenerative diseases.The study demonstrates how ATP, the energy currency of cells, influences the progression of conditions like Alzheimer’s and Parkinson’s. Discoveries point to a potential pathway for new treatments.
Atp’s Surprising Role in Neurodegenerative Diseases: A New path to Treatment?
Neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis (ALS), affect millions globally, presenting formidable challenges in prevention and treatment. These conditions involve a complex interplay of genetic predispositions, lifestyle factors, and othre influences, complicating both diagnosis and therapeutic interventions.
The Energy Molecule’s Unexpected Function
Scientists are making strides in understanding the fundamental characteristics of these neurological conditions, offering hope for preventing or alleviating cognitive and motor impairments.A recent study published in Science advances sheds light on the surprising role of adenosine triphosphate (ATP), commonly known as the ‘fuel’ of our cells, in neurodegenerative processes [[2]].
Mitochondria, the powerhouses of our cells, are critical in ATP synthesis and play a significant role in neurodegenerative diseases by modulating apoptosis, ferroptosis, and inflammasome activation [[1]].
Dr. Laurent Guillaud, lead author of the study, stated, We found that ATP regulates protein condensation and the overall viscosity of cytoplasm in neurons.
This discovery highlights ATP’s influence on the axoplasm, the cytoplasm within axons.When the axoplasm becomes more viscous, proteins are more likely to aggregate, perhaps forming harmful tangles that damage cells [[2]].
Through both in vitro and in vivo trials, we found that boosting ATP production decreases cytosolic viscosity in affected cells, dispersing existing and preventing future pathological protein aggregations.
Dr. Laurent Guillaud
Protein Aggregation: A Common Thread
A hallmark of many neurodegenerative diseases is the formation and accumulation of insoluble, membrane-less protein condensates through liquid-liquid phase separation. These protein aggregates can accumulate both inside and outside cells, manifesting as neurofibrillary tangles in late-stage Alzheimer’s disease.
Atp as a Hydrotropic Agent
Recent research indicates that ATP directly regulates protein solubilization in vitro and cytoplasmic viscosity in yeast cells, functioning as a hydrotropic agent. Hydrotropic agents increase the solubility of poorly water-soluble substances, including various proteins. The team’s experiments on human stem cell-derived neurons from healthy individuals and patients with parkinson’s and ALS revealed a direct relationship between intracellular ATP concentration and the solubility of the axoplasm and proteins associated with neurodegenerative disorders, such as SNCA in Parkinson’s, Tau in Alzheimer’s, and TDP-43 in ALS.
Maintaining healthy mitochondrial function is crucial for ATP production. Lifestyle choices, such as diet and exercise, can significantly impact mitochondrial health.
Dr. Guillaud explained:
Mammalian cells normally have an average ATP concentration of four to eight millimolar,which is surprisingly high,as the total concentration of ATP needed for all energy processes in the cell is only in the few hundreds of micromolar — an order of magnitude lower. This led us to focus on and examine the possible hydrotropic role of ATP in neurons,from which we found a remarkable correlation between the intracellular concentration of ATP and the axoplasmic viscosity in both physiological and pathological conditions.
Dr. Laurent Guillaud
The researchers demonstrated that local variations in ATP could affect the viscosity of the cytosol, synaptic vesicles, and active zones in the presynaptic compartment, altering the functional association of the synapse.
Mitochondrial Health and Atp Production
Mitochondria are the primary producers of ATP, and their function naturally declines with age. Factors that negatively affect mitochondrial health, such as those present in Parkinson’s disease or ALS, can further reduce ATP concentration, decreasing protein solubility and increasing cytoplasmic viscosity. The researchers found that boosting ATP production using nicotinamide mononucleotide (NMN) rescued cytosolic fluidity by breaking up and solubilizing existing protein aggregates in axons from ALS neurons.
Implications and future Directions
Research into neurodegenerative diseases is inherently complex, given their multifaceted nature. While a comprehensive cure remains elusive, these findings offer crucial insights into the cellular mechanisms of these diseases. These advances bring us closer to potentially preventing or treating these debilitating neurodegenerative disorders comprehensively.
Frequently Asked Questions (FAQ)
- What is ATP? ATP, or adenosine triphosphate, is the primary energy carrier in cells.
- How dose ATP relate to neurodegenerative diseases? ATP regulates protein condensation and the viscosity of cytoplasm in neurons,affecting protein aggregation.
- What role do mitochondria play? Mitochondria produce ATP, and their health is crucial for maintaining adequate ATP levels in cells.
- Can ATP production be boosted? Yes,interventions like NMN supplementation have shown promise in boosting ATP production and improving cytosolic fluidity.
