Objective: To evaluate neuroprotective role of baicalein via autophagy mediated modulation of associated motor proteins in rotenone induced mice model of Parkinson disease.

Background: Parkinson’s disease (PD), as the second most prevalent neurological disorder, is associated with a wide range of molecular insults that contribute to its etiology. Microtubule-assisted axonal transport, an invaluable necessity for cargo commute and autophagy, is also found compromised in PD. Apart from orchestrating the transport of vital cargoes, the motor proteins also tightly regulate autophagy, a process responsible for the clearance of α-Synuclein aggregates and other damaged cargoes.

Method: In the present study, C57BL6 mice were induced PD with single dose of rotenone (1 μg i.c.v.) and concomitant administration of baicalein (75 and 125 mg/g p.o.) for 28 days. Various behvioural (Rotarod and Actimeter) assessments were done on 0 day (Baseline) and on 28 days of the study (End point). In addition to drawing molecular mechanisms, we performed molecular studies including western blot (α syn, TH, KIF5B, Dynein, Dynactin, α/β tubulin, LC3 and, p62), and immunohistochemistry studies (TH positive neurons).

Results: The results showed increasing the expression of profound microtubule affiliated motor proteins of the anterograde (KIF5B) and retrograde (dynein and dynactin) system, baicalein promotes the chances of autophagy by enabling better movement of the autophagosomes towards the lysosomes and their active recycling for appropriate turnover. Our novel research establishes an affirmative link between baicalein-induced autophagy and microtubule affiliated motor proteins in direct variation.

Conclusion: Taken together, our work indicates that modulating the motor proteins can have a fundamental impact in enhancing autophagy and autophagy-augmenting therapies can focus on elevating motor proteins for better impact.

Graphical abstract

References: [1] Naren P, Samim KS, Tryphena KP, Vora LK, Srivastava S, Singh SB, et al. Microtubule acetylation dyshomeostasis in Parkinson’s disease. Transl Neurodegener. 2023;12:20. Available from: https://doi.org/10.1186/s40035-023-00354-0

[2] Gonzalez AE, Wang X. Drosophila VCP/p97 Mediates Dynein-Dependent Retrograde Mitochondrial Motility in Axons. Front cell Dev Biol. 2020;8:256.

[3] Chen M, Peng L, Gong P, Zheng X, Sun T, Zhang X, et al. Baicalein Mediates Mitochondrial Autophagy via miR-30b and the NIX/BNIP3 Signaling Pathway in Parkinson’s Disease. Biochem Res Int. United States; 2021;2021:2319412.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroprotective-role-of-baicalein-via-autophagy-mediated-modulation-of-associated-motor-proteins-in-experimental-animals-of-parkinson-disease/