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Review
. 2024 Jul 3;44(1):53.
doi: 10.1007/s10571-024-01471-8.

Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease

Twinkle Mishra  1 , Shareen Singh  1 , Thakur Gurjeet Singh  2
Affiliations
Review

Therapeutic Implications and Regulations of Protein Post-translational Modifications in Parkinsons Disease

Twinkle Mishra et al. Cell Mol Neurobiol. .

Abstract

Parkinsons disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and alpha-synuclein aggregation. This comprehensive review examines the intricate role of post-translational modifications (PTMs) in PD pathogenesis, focusing on DNA methylation, histone modifications, phosphorylation, SUMOylation, and ubiquitination. Targeted PTM modulation, particularly in key proteins like Parkin, DJ1, and PINK1, emerges as a promising therapeutic strategy for mitigating dopaminergic degeneration in PD. Dysregulated PTMs significantly contribute to the accumulation of toxic protein aggregates and dopaminergic neuronal dysfunction observed in PD. Targeting PTMs, including epigenetic strategies, addressing aberrant phosphorylation events, and modulating SUMOylation processes, provides potential avenues for intervention. The ubiquitin-proteasome system, governed by enzymes like Parkin and Nedd4, offers potential targets for clearing misfolded proteins and developing disease-modifying interventions. Compounds like ginkgolic acid, SUMO E1 enzyme inhibitors, and natural compounds like Indole-3-carbinol illustrate the feasibility of modulating PTMs for therapeutic purposes in PD. This review underscores the therapeutic potential of PTM-targeted interventions in modulating PD-related pathways, emphasizing the need for further research in this promising area of Parkinsons disease therapeutics.

Keywords: Dopaminergic degeneration; PTM-targeted interventions; Parkinsons disease; Post-translational modifications; Protein aggregates.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of accumulation of misfolded proteins involved in neurodegeneration in PD
Fig. 2
Fig. 2
Representation of abnormal pathogenic proteins (Alpha-synuclein, PTEN-induced kinase 1 (PINK1), Parkin, TOM20) confirmations linked involvement of post-transitional modifications directly regulating further intracellular cascades of NB and apoptosis mediated neurodegeneration of PD
See this image and copyright information in PMC

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