Understanding Abscisic Acid\'s Impact on Parkinson’s Neuroinflammation

Pirilinu Sakellari^*
*Correspondence: Pirilinu Sakellari, Department of Psychology, University of Turin, 10124 Turin, Italy, Email:

Introduction

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as tremors, rigidity and bradykinesia, as well as non-motor symptoms including cognitive impairment and autonomic dysfunction. While the exact etiology of PD remains elusive, accumulating evidence suggests that neuroinflammation plays a pivotal role in disease pathogenesis and progression. Neuroinflammation, characterized by the activation of microglia and astrocytes and the release of pro-inflammatory cytokines and chemokines, contributes to neuronal damage and dysfunction in PD, exacerbating dopaminergic neurodegeneration and clinical symptoms [1].

Abnormalities in immune signaling pathways have been implicated in the pathogenesis of PD, highlighting the potential therapeutic relevance of targeting neuroinflammatory processes to slow disease progression. In recent years, Abscisic Acid (ABA), a phytohormone best known for its role in plant stress responses, has emerged as a novel regulator of neuroinflammation with promising therapeutic potential in PD. A growing body of research suggests that ABA exerts anti-inflammatory and neuroprotective effects in the Central Nervous System (CNS), modulating microglial activation, cytokine production and oxidative stress pathways. This comprehensive discourse seeks to elucidate the impact of ABA on Parkinson’s neuroinflammation, encompassing an introduction to PD pathophysiology, the role of neuroinflammation in disease progression, the biology of ABA, experimental evidence supporting its anti-inflammatory effects, translational implications and avenues for future research [2].

Description

Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in striatal dopamine depletion and the emergence of motor and non-motor symptoms. While the precise etiology of PD remains incompletely understood, a complex interplay of genetic susceptibility, environmental factors, mitochondrial dysfunction and protein aggregation is thought to underlie disease pathogenesis. Accumulating evidence suggests that neuroinflammation contributes to the progressive nature of PD, exacerbating dopaminergic neurodegeneration through the release of inflammatory mediators and the activation of immune cells within the CNS. Neuroinflammation in PD is characterized by the activation of microglia, the resident immune cells of the CNS and astrocytes, the most abundant glial cells, leading to the release of pro-inflammatory cytokines (e.g., interleukin-1β, tumor necrosis factor-α), chemokines and Reactive Oxygen Species (ROS). These inflammatory mediators contribute to the amplification of neuroinflammatory cascades, recruitment of peripheral immune cells into the brain parenchyma and disruption of the blood-brain barrier, further exacerbating neuronal damage and dysfunction. Additionally, neuroinflammation in PD is closely linked to the aggregation of misfolded proteins, such as α-synuclein, into insoluble fibrillary aggregates, which trigger innate immune responses and perpetuate neuroinflammatory processes [3].

Aberrant immune signaling pathways implicated in PD pathogenesis represent attractive targets for therapeutic intervention aimed at modulating neuroinflammatory responses and preserving dopaminergic function. Abscisic Acid (ABA), a phytohormone originally identified as a regulator of plant growth and stress responses, has recently garnered attention for its anti-inflammatory properties in the CNS. ABA acts through binding to its cognate receptor, Pyrabactin Resistance 1 (PYR1)/PYR1-LIKE (PYL)/Regulatory Component of ABA Receptor (RCAR), leading to the inhibition of the Protein Phosphatase type 2C (PP2C) and the activation of SNF1-Related Protein Kinase2s (SnRK2s), which in turn regulate downstream signaling pathways involved in stress responses, metabolism and immune function. Experimental evidence from preclinical studies supports the anti-inflammatory and neuroprotective effects of ABA in various models of neurodegenerative diseases, including PD. ABA has been shown to attenuate microglial activation and pro-inflammatory cytokine production, reduce oxidative stress and neuronal apoptosis and preserve dopaminergic function in animal models of PD. Moreover, ABA exhibits pleiotropic effects on cellular pathways implicated in neuroinflammation, including Nuclear Factor-kappa B (NF-κB) signaling, Mitogen-Activated Protein Kinase (MAPK) pathways and inflammasome activation, suggesting its potential as a multifaceted therapeutic agent for PD [4].

Translating the promising preclinical findings on ABA into clinical applications for PD represents a significant challenge and opportunity in translational neuroscience. While ABA exhibits favorable pharmacokinetic properties, including blood-brain barrier permeability and metabolic stability, its clinical development as a neuroprotective therapy for PD requires rigorous evaluation of safety, efficacy and optimal dosing regimens in human clinical trials. Furthermore, elucidating the precise mechanisms underlying ABA's anti-inflammatory effects in the CNS and its interactions with other signaling pathways implicated in PD pathogenesis will be critical for optimizing therapeutic strategies and identifying patient populations most likely to benefit from ABA-based interventions [5].

Conclusion

In conclusion, neuroinflammation represents a promising target for therapeutic intervention in Parkinson's disease, with growing evidence implicating Abscisic Acid (ABA) as a novel regulator of neuroinflammatory processes with potential neuroprotective effects. ABA's anti-inflammatory properties, mediated through its interaction with ABA receptors and downstream signaling pathways, hold promise for mitigating neuroinflammation-induced dopaminergic neurodegeneration and slowing disease progression in PD. However, translating the preclinical findings on ABA into effective clinical therapies for PD requires further investigation, including rigorous evaluation of safety, efficacy and mechanisms of action in human clinical trials. Through collaborative efforts between basic scientists, clinicians and industry stakeholders, ABA-based interventions may offer new avenues for improving outcomes in Parkinson's disease and addressing the unmet needs of patients affected by this debilitating neurodegenerative disorder.

Acknowledgement

None.

Conflict of Interest

None.

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