Objective: The study aimed to delineate the molecular mechanism involved in bidirectional olfactory-brain dysfunction through the NLRP3 inflammasome signaling activation in in-vitro and in-vivo model of PD.

Background: The NLRP3 inflammasome signaling cascade activation is a significant contributor to the initiation and progression of Parkinson’s disease (PD) [1]. Recent evidence supports that targeting NLRP3 inflammasome assembly could be a potential strategy to halt PD progression. The molecular mechanism of the bidirectional olfactory-brain axis in mediating PD remains elusive [2, 3].

 ​​​​​​​

Method: The current study aimed to investigate: a) the potential effect of Loganic acid (LA) in inhibiting the NLRP3 inflammasome signaling, microglial activation and promoting neurogenesis through molecular docking and in in-vitro experiments. b) to delineate the mechanism of bidirectional olfactory-brain dysfunction through the NLRP3 inflammasome signaling activation in in-vivo model of PD and explore the role of LA.

Results: Our results in in-vitro studies demonstrated that LA treatment in MPP⁺-induced microglial cells inhibits NLRP3 inflammasome assembly, halts phagocytosis, and downregulates the release of pro-inflammatory cytokines such as IL-1β and IL-18. Further, results confirm that LA increases the neuronal differentiation markers and assists neurite growth. To correlate the in-vitro experiments with the in-vivo study, LA treatment prevented the loss of olfactory and motor function. In immunoblotting, LA treatment significantly inhibits the expression of NLRP3 inflammasome signaling cascade when compared to the MPTP group of the olfactory bulb and substantia nigra. Molecular docking data of LA on IL-β, NLRP3, caspase-1, and ASC also supports strong evidence in the downregulation of inflammasome and cytokines through potential non-covalent Interactions.

Conclusion:

Loganic acid treatment showed a prominent neuroprotective effect via regulating cellular redox homeostasis, restricting microglial activation, and supporting neuronal survival by targeting the NLRP3 inflammasome pathway in both cellular and animal model and further reducing neuroinflammation and neuronal damage associated with PD.

References: [1] Ahmed S, Panda SR, Kwatra M, Sahu BD, Naidu VJAcn (2021a) Perillyl alcohol attenuates NLRP3 inflammasome activation and rescues dopaminergic neurons in experimental in vitro and in vivo models of parkinson’s disease. 13:53-68.
[2] Ahmed S, Kwatra M, Gawali B, Panda SR, Naidu VJA (2021b) Potential role of TrkB agonist in neuronal survival by promoting CREB/BDNF and PI3K/Akt signaling in vitro and in vivo model of 3-nitropropionic acid (3-NP)-induced neuronal death. 26:52-70.
[3] Ahmed S, Kwatra M, Panda SR, Murty U, Naidu VJB, behavior,, immunity (2021c) Andrographolide suppresses NLRP3 inflammasome activation in microglia through induction of parkin-mediated mitophagy in in-vitro and in-vivo models of Parkinson disease. 91:142-158.

« Back to 2024 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/loganic-acid-alleviates-the-bidirectional-olfactory-brain-nlrp3-inflammasome-activation-and-rescues-dopaminergic-neurons-in-experimental-models-of-parkinsons-disease/